BronchitisBronchitis is an inflammation of the mucous membranes of the deep inner lung passages called the bronchial tree.

Bronchitis may be either acute or chronic. Acute bronchitis is frequently caused by a viral or bacterial infection. Acute bronchitis may also result from irritation of the mucous membranes by environmental fumes, acids, solvents, or tobacco smoke. Bronchitis usually begins with a dry, nonproductive cough. After a few hours or days, the cough may become more frequent and produce mucus. A secondary bacterial infection may occur, in which the sputum (bronchial secretions) may contain pus. People whose cough and/or fever continues for more than seven days should visit a medical practitioner.

Chronic bronchitis may result from prolonged exposure to bronchial irritants. Cigarette smoking, environmental toxins, and inhaled allergens can all cause chronic irritation of the bronchi. The cells lining the bronchi produce excess mucus in response to the chronic irritation; this excess mucus production can lead to a chronic, productive cough.

Bronchitis can be particularly dangerous in the elderly and in people with compromised immune systems. These people should see a doctor if they develop a respiratory infection.

What are the symptoms of bronchitis?

Acute infectious bronchitis is often preceded by signs of an upper respiratory tract infection: stuffy or runny nose, malaise, chills, fever, muscle pain, and sore throat. The cough is initially dry and does not produce mucus. Later, small amounts of thick green or green-yellow sputum may be coughed up.

Chronic bronchitis is characterized by a productive cough that initially occurs only in the morning.

Medical treatments

Over the counter drugs used to treat the symptoms of bronchitis include the expectorant guaifenesin (Robitussin®) and the cough suppressant dextromethorphan (DM), which are usually found in combination (Robitussin DM®, Vicks 44E Liquid®, Benylin Expectorant Liquid®).

Antibiotics, which require a prescription, are used when the sputum becomes dark green or yellow, indicating a bacterial infection. Agents used include the tetracycline doxycycline (Vibramycin®), trimethoprim/sulfamethoxazole (Bactrim®, Septra®), amoxicillin/clavulanate (Augmentin®), and azithromycin (Zithromax®). Symptomatic treatment of cough may be given to aid sleep; however daytime use of antitussives (cough suppressants) should be limited in order to clear infected mucous from the lungs. Antitussives that require a prescription include codeine (Robitussin A-C Syrup®) and hydrocodone (Vicodin Tuss Syrup®, Tussionex®).

Rest and increased fluid intake are recommended in the fever stage of acute bronchitis. Treatment of chronic bronchitis includes smoking cessation and a variety of drugs directed at relieving symptoms and treating superimposed bacterial infections.

Dietary changes that may be helpful

Dietary factors may influence both inflammatory activity and antioxidant status in the body. Increased inflammation and decreased antioxidant activity may each lead to an increased incidence of chronic diseases, such as chronic bronchitis. People suffering from chronic bronchitis may experience an improvement in symptoms when consuming a diet high in anti-inflammatory fatty acids, such as those found in fish. In a double-blind study of children with recurrent respiratory tract infections, a daily essential-fatty-acid supplement (containing 855 mg of alpha-linolenic acid and 596 mg of linoleic acid) reduced both the number and the duration of recurrences.1

In people with bronchitis, lipids in the lung tissue may undergo oxidation damage (also called free-radical damage), particularly when the bronchitis is a result of exposure to environmental toxins or cigarette smoke. A diet high in antioxidants may protect against the free radical-damaging effect of these toxins. Studies comparing different populations have shown that increasing fruit and vegetable (and therefore, antioxidant) consumption may reduce the risk of developing chronic bronchitis.2 3

Food and environmental allergies may be triggering factors in some cases of chronic bronchitis.4 Cows’ milk allergy has been associated with bronchitis in children,5 6 7 and some doctors believe that dairy products may increase mucus production and, therefore, that people suffering from either acute or chronic bronchitis should limit their intake of dairy products. Ingestion of simple sugars (such as sucrose or fructose) can lead to suppression of immune function;8 therefore, some doctors believe simple sugars should be avoided during illness.

Lifestyle changes that may be helpful

Breast-feeding provides important nutrients to an infant and improves the functioning of the immune system. Studies have shown that breast-feeding prevents the development of lower respiratory tract infections during infancy.9 10 Whether that protective effect persists into adulthood is not known. Exposure to environmental chemicals, including passive smoke, can increase the incidence of respiratory illness among children.11

Chronic bronchitis is frequently associated with smoking and/or environmental exposure to chemicals or allergens. These exposures should be avoided to allow the cells of the bronchi to recover from chronic irritation and to decrease the burden on the immune system.

Nutritional supplements that may be helpful

In a double-blind study of elderly patients hospitalized with acute bronchitis, those who were given 200 mg per day of vitamin C improved to a significantly greater extent than those who were given a placebo.12 The common cold may lead to bronchitis in susceptible people, and

numerous controlled studies, some double-blind, have shown that vitamin C supplements can decrease the severity and duration of the common cold in otherwise healthy people.13

Vitamin C and vitamin E may prevent oxidative damage to the lung lipids by environmental pollution and cigarette smoke exposure. It has been suggested that amounts in excess of the RDA (recommended dietary allowance) are necessary to protect against the air pollution levels currently present in North America,14 although it is not known how much vitamin E is needed to produce that protective effect.

A review of 39 clinical trials of N-acetyl cysteine (NAC) found that 400 to 600 mg per day was a safe and effective treatment for chronic bronchitis.15 NAC supplementation was found to reduce the number of aggravations of the illness in almost 50% of people taking the supplement, compared with only 31% of those taking placebo. Smokers have also been found to benefit from taking NAC.16 In addition to helping break up mucus, NAC may reduce the elevated bacterial counts that are often seen in the lungs of smokers with chronic bronchitis.17 In another double-blind study, people with chronic bronchitis who took NAC showed an improved ability to expectorate and a reduction in cough severity.18 These benefits may result from NAC’s capacity to reduce the viscosity (thickness) of sputum.19

Vitamin A levels are low in children with measles,20 an infection that can result in pneumonia or other respiratory complications. A number of studies have shown that supplementation with vitamin A decreased complications and deaths from measles in children living in developing countries where deficiencies of vitamin A are common.21 However, little to no positive effect, and even slight adverse effects, have resulted from giving vitamin A supplements to prevent or treat infections in people living in countries where most people consume adequate amounts of vitamin A.22 23 24 25 26 27 Therefore, vitamin A supplements may only be useful for people with bronchial infections who are known to be deficient in vitamin A.

The thymus gland plays a number of important roles in the functioning of the immune system. Thymus extract from calves, known as Thymomodulin®, has been found, in a double-blind study, to decrease the frequency of respiratory infections in children who were prone to such infections.28 The amount of Thymomodulin used in that study was 3 mg per kg of body weight per day.

Are there any side effects or interactions?Refer to the individual supplement for information about any side effects or interactions.

Herbs that may be helpful

Several types of herbs may help people with bronchitis, either by treating underlying infection, by relieving inflammation, or by relieving symptoms such as cough. For clarity, the table below summarizes which herbs are in each category of action. Some herbs have more than one action. Herbs listed in the table have not necessarily been proven to be effective. The herbs are discussed in more detail following the table.

Action Botanicals Supported by Clinical Trials Botanicals Used Traditionally

Expectorant (helps remove mucus) Anise, horehound, horseradish,

mullein, pleurisy root

Anti-inflammatory Chinese scullcap, ivy leaf, plantain Elecampane, marshmallow, mullein, slippery elm

Fights infection Echinacea (by stimulating immune system), lavender, thyme Eucalyptus, horseradish

Antitussive (relieves cough) Lobelia, marshmallow

Relieves bronchospasms or spasmodic cough Lobelia, thyme

Expectorant herbs help loosen bronchial secretions and make elimination of mucus easier. Numerous herbs are traditionally considered expectorants, though most of these have not been proven to have this effect in clinical trials. Anise contains a volatile oil that is high in the chemical constituent anethole and acts as an expectorant.29

Horehound has expectorant properties, possibly due to the presence of a diterpene lactone in the plant, which is known as marrubiin.30

Mullein has been used traditionally as a remedy for the respiratory tract, including bronchitis. The saponins in mullein may be responsible for its expectorant actions.31

Pleurisy root is an expectorant and is thought to be helpful against all types of respiratory infections. It is traditionally employed as an expectorant for bronchitis. However, owing to the cardiac glycosides it contains, pleurisy root may not be safe to use if one is taking (heart medications.32 This herb should not be used by pregnant women.

Anti-inflammatory herbs may help people with bronchitis. Often these herbs contain complex polysaccharides and have a soothing effect; they are also known as demulcents. Plantain is a demulcent that has been documented in two preliminary trials conducted in Bulgaria to help people with chronic bronchitis.33 34 Other demulcents traditionally used for people with bronchitis include mullein, marshmallow, and slippery elm. Because demulcents can provoke production of more mucus in the lungs, they tend to be used more often in people with dry coughs.35

Elecampane is a demulcent that has been used to treat coughs associated with bronchitis, asthma, and whooping cough. Although there have been no modern clinical studies with this herb, its use for these indications is based on its high content of soothing mucilage in the forms of inulin and alantalactone.36 However, the German Commission E monograph for elecampane does not approve the herb for bronchitis.37

Ivy leaf is approved in the German Commission E monograph for use against chronic inflammatory bronchial conditions.38 One double-blind human trial found ivy leaf to be as effective as the drug ambroxol for chronic bronchitis.39 Ivy leaf is a non-demulcent anti-inflammatory.

Chinese scullcap might be useful for bronchitis as an anti-inflammatory. However, the research on this herb is generally of low quality.40

Antimicrobial and immune stimulating herbs may also potentially benefit people with bronchitis. Echinacea is widely used by herbalists for people with acute respiratory infections. This herb stimulates the immune system in several different ways, including enhancing macrophage function and increasing T-cell response.41 Therefore, echinacea may be useful for preventing a cold, flu, or viral bronchitis from progressing to a secondary bacterial infection.

Thyme contains an essential oil (thymol) and certain flavonoids. This plant has antispasmodic, expectorant, and antibacterial actions, and it is considered helpful in cases of bronchitis.42 One preliminary trial found that a mixture containing volatile oils of thyme, mint, clove, cinnamon, and lavender diluted in alcohol, in the amount of 20 drops three times daily, reduced the number of recurrent infections in people with chronic bronchitis.43

Horseradish contains substances similar to mustard, such as glucosinolates and allyl isothiocynate.44 In addition to providing possible antibacterial actions, these substances may also have expectorant properties that are supportive for persons with bronchitis.

Eucalyptus leaf tea is used to treat bronchitis and inflammation of the throat,45 and is considered antimicrobial. In traditional herbal medicine, eucalyptus tea or volatile oil is often used internally as well as externally over the chest; both uses are approved for people with bronchitis by the German Commission E.46

Lobelia contains many active alkaloids, of which lobeline is considered the most active. Very small amounts of this herb are considered helpful as an antispasmodic and antitussive agent (a substance that helps suppress or ease coughs). Anti-inflammatory properties of the herb have been demonstrated, which may be useful, since bronchitis is associated with inflammation in the bronchi.47 Lobelia should be used cautiously, as it may cause nausea and vomiting.

Are there any side effects or interactions?Refer to the individual herb for information about any side effects or interactions.

References

1. Venuto A, Spano C, Laudizi L, Bettelli F. Essential fatty acids: the effects of dietary supplementation among children with recurrent respiratory infections. J Intl Med Res 1996;24:325–30.

2. La Vecchia C, Decarli A, Pagano R. Vegetable consumption and risk of chronic disease. Epidemiology 1998;9:208–10.

3. Rautalahti M, Virtamo J, Haukka J, et al. The effect of alpha-tocopherol and beta-carotene supplementation on COPD symptoms. Am J Respir Crit Care Med 1997;156:1447–52.

4. Rowe AH, Rowe A. Food Allergy: its role in emphysema and chronic bronchitis. Dis Chest 1965;48:609–12.

5. Hill DJ, Duke AM, Hosking CS, Hudson IL. Clinical manifestations of cows’ milk allergy in childhood. II. The diagnostic value of skin tests and RAST. Clin Allergy 1988;18:481–90.

6. Cohen GA, Hartman G, Hamburger RN, O’Connor RD. Severe anemia and chronic bronchitis associated with a markedly elevated specific IgG to cow’s milk protein. Ann Allergy 1985;55:38–40.

7. Hide DW, Guyer BM. Clinical manifestations of allergy related to breast and cows’ milk feeding. Arch Dis Child 1981;56:172–5.

8. Sanchez A, Reeser JL, Lau HS, et al. Role of sugars in human neutrophilic phagocytosis. Am J Clin Nutr 1973;26:1180–4.

9. Pisacane A, Graziano L, Zona G, et al. Breast feeding and acute lower respiratory infection. Acta Paediatr 1994;83:714–8.

10. Kerr AA. Lower respiratory tract illness in Polynesian infants. New Zealand Med J 1981;93:333–5.

11. Jin C, Rossignol AM. Effects of passive smoking on respiratory illness from birth to age eighteen months, in Shanghai, People’s Republic of China. J Pediatr 1993;123:553–8.

12. Hunt C, Chakravorty NK, Annan G, et al. The clinical effects of vitamin C supplementation in elderly hospitalised patients with acute respiratory infections. Int J Vitam Nutr Res 1994;64:212–9.

13. Hemilä H. Does vitamin C alleviate the symptoms of the common cold?—A review of current evidence. Scand J Infect Dis 1994;26:1–6.

14. Menzel DB. Antioxidant vitamins and prevention of lung disease.Ann N Y Acad Sci 1992;669:141–55.

15. Stey C, Steurer J, Bachmann S, et al. The effect of oral N-acetylcysteine in chronic bronchitis: a quantitative systematic review. Eur Respir J 2000;16:253–62 [review].

16. Boman G, Backer U, Larsson S, et al. Oral acetylcysteine reduces exacerbation rate in chronic bronchitis: report of a trial organized by the Swedish Society for Pulmonary Diseases. Eur J Respir Dis 1983;64:405–15.

17. Riise GC, Larsson S, Larsson P, et al. The intrabronchial microbial flora in chronic bronchitis patients: a target for N-acetylcysteine therapy? Eur Respir J 1994;7:94–101.

18. Jackson IM, Barnes J, Cooksey P. Efficacy and tolerability of oral acetylcysteine (Fabrol) in chronic bronchitis: a double-blind placebo controlled study. J Int Med Res 1984;12:198–206.

19. Tattersall AB, Bridgman KM, Huitson A. Acetylcysteine (Fabrol) in chronic bronchitis—a study in general practice. J Int Med Res 1983;11:279–84.

20. Arrieta AC, Zaleska M, Stutman HR, Marks MI. Vitamin A levels in children with measles in Long Beach, California. J Pediatr 1992;121:75–8.

21. Fawzi WW, Chalmers TC, Herrera MG, Mosteller F. Vitamin A supplementation and child mortality. A meta-analysis. JAMA 1993;269:898–903.

22. Stephensen CB, Franchi LM, Hernandez H, et al. Adverse effects of high-dose vitamin A supplements in children hospitalized with pneumonia. Pediatrics 1998;101(5):E3 [abstract].

23. Bresee JS, Fischer M, Dowell SF, et al. Vitamin A therapy for children with respiratory syncytial virus infection: a multicenter trial in the United States. Pediatr Infect Dis J 1996;15:777–82.

24. Quinlan KP, Hayani KC. Vitamin A and respiratory syncytial virus infection. Serum levels and supplementation trial. Arch Pediatr Adolesc Med 1996;150:25–30.

25. Kjolhede CL, Chew FJ, Gadomski AM, et al. Clinical trial of vitamin A as adjuvant treatment for lower respiratory tract infections. J Pediatr 1995;126:807–12.

26. Pinnock CB, Douglas RM, Badcock NR. Vitamin A status in children who are prone to respiratory tract infections. Aust Paediatr J 1986;22:95–9.

27. Murphy S, West KP Jr, Greenough WB 3d, et al. Impact of vitamin A supplementation on the incidence of infection in elderly nursing-home residents: a randomized controlled trial. Age Ageing 1992;21:435–9.

28. Fiocchi A, Borella E, Riva E, et al. Double-blind clinical trial for the evaluation of the therapeutical effectiveness of a calf thymus derivative (Thymomodulin) in children with recurrent respiratory infections. Thymus 1986;8:331–9.

29. Schulz V, Hänsel R, Tyler VE. Rational Phytotherapy: A Physicians’ Guide to Herbal Medicine. Berlin: Springer-Verlag, 1998, 159–60.

30. Leung AY, Foster S. Encyclopedia of Common Natural Ingredients Used in Food, Drugs, and Cosmetics, 2d ed. New York: John Wiley, 1996, 303.

31. Foster S, Tyler VE. Tyler’s Honest Herbal. New York: Haworth Press, 1999, 2265–6.

32. Newall CA, Anderson LA, Phillipson JD. Herbal Medicine: A Guide for Health-Care Professionals. London: Pharmaceutical Press, 1996, 213–4.

33. Koichev A. Complex evaluation of the therapeutic effect of a preparation from Plantago major in chronic bronchitis. Probl Vatr Med 1983;11:61–9 [in Bulgarian].

34. Matev M, Angelova I, Koichev A, et al. Clinical trial of Plantago major preparation in the treatment of chronic bronchitis. Vutr Boles 1982;21:133–7 [in Bulgarian].

35. Mills S, Bone K. Principles and Practice of Phytotherapy: Modern Herbal Medicine. Edinburgh: Churchill Livingstone, 2000, 209.

36. Wichtl M. Herbal Drugs and Phytopharmaceuticals. Boca Raton, FL: CRC Press, 1994, 254–6.

37. Blumenthal M, Busse WR, Goldberg A, et al, eds. The Complete German Commission E Monographs: Therapeutic Guide to Herbal Medicines. Newton, MA: Integrative Medicine Communications, 1998, 328–9.

38. Blumenthal M, Busse WR, Goldberg A, et al, eds. The Complete German Commission E Monographs: Therapeutic Guide to Herbal Medicines. Boston, MA: Integrative Medicine Communications, 1998, 153.

39. Meyer-Wegner J. Ivy versus ambroxol in chronic bronchitis. Zeits Allegemeinmed 1993;69:61–6 [in German].

40. Bone K, Morgan M. Clinical Applications of Ayurvedic and Chinese Herbs: Monographs for the Western Herbal Practitioner. Warwick, Australia: 1996.

41. See DM, Broumand N, Sahl L, Tilles JG. In vitro effects of echinacea and ginseng on natural killer and antibody-dependent cell cytotoxicity in healthy subjects and chronic fatigue syndrome or acquired immunodeficiency syndrome patients. Immunopharmacol 1997;35:229–35.

42. Blumenthal M, Busse WR, Goldberg A, et al. The Complete German Commission E Monographs: Therapeutic Guide to Herbal Medicines. Newton, MA: Integrative Medicine Communications, 1998, 219–20.

43. Ferley JP, et al. Prophylactic aromatherapy for supervening infections in patients with chronic bronchitis. Phytother Res 1989;3:97–9.

44. Blumenthal M, Goldberg A, Brinkman J, eds. Herbal Medicine: The Expanded Commission E Monographs. Newton, MA: Integrative Medicine Communications, 2000, 205–7.

45. Wichtl M. Herbal Drugs and Phytopharmaceuticals. Boca Raton, FL: CRC press, 1994,192–4.

46. Blumenthal M, Busse WR, Goldberg A, et al, eds. The Complete German Commission E Monographs: Therapeutic Guide to Herbal Medicines. Newton, MA: Integrative Medicine Communications, 1998, 126–8.

47. Philipov S, Istatkova R, Ivanovska N, et al. Phytochemical study and antiinflammatory properties of Lobelia laxiflora L. Z Naturforsch (C) 1998;53:311–7.

http://www.puritan.com/vf/healthnotes/HN_live/Concern/Bronchitis.htm Retrieved April 18 , 2011

Bronchitis Author: Jazeela Fayyaz, DO; Chief Editor: Zab Mosenifar, MD mor

BackgroundBronchitis is one of the top conditions for which patients seek medical care. It is characterized by inflammation of the bronchial tubes (or bronchi), the air passages that extend from the trachea into the small airways and alveoli. (See Clinical Presentation.)

Chronic bronchitis is defined clinically as cough with sputum expectoration for at least 3 months a year during a period of 2 consecutive years. Chronic bronchitis is associated with hypertrophy of the mucus-producing glands found in the mucosa of large cartilaginous airways. As the disease advances, progressive airflow limitation occurs, usually in association with pathologic changes of emphysema. This condition is called chronic obstructive pulmonary disease. (See Clinical Presentation.)

When a stable patient experiences sudden clinical deterioration with increased sputum volume, sputum purulence, and/or worsening of shortness of breath, this is referred to as an acute exacerbation of chronic bronchitis, as long as conditions other than acute tracheobronchitis are ruled out. (See Diagnosis.)

Triggers of bronchitis may be infectious agents, such as viruses or bacteria, or noninfectious agents, such as smoking or inhalation of chemical pollutants or dust. Bronchitis typically occurs in the setting of an upper respiratory illness; thus, it is observed more frequently in the winter months. (See Etiology.)

Allergens and irritants can produce a similar clinical picture. Asthma can be mistakenly diagnosed as acute bronchitis if the patient has no prior history of asthma. In one study, one third

of patients who had been determined to have recurrent bouts of acute bronchitis were eventually identified as having asthma. Generally, bronchitis is a diagnosis made by exclusion of other conditions such as sinusitis, pharyngitis, tonsillitis, and pneumonia. (See Diagnosis.)

Acute bronchitis is manifested by cough and, occasionally, sputum production that last for no more than 3 weeks. Although bronchitis should not be treated with antimicrobials, it is frequently difficult to refrain from prescribing them. Accurate testing and decision-making protocols regarding who might benefit from antimicrobial therapy would be useful but are not currently available. (See Treatment and Management, as well as Medication.)

To see complete information on Pediatric Bronchitis, please go to the main article by clicking here.

PathophysiologyDuring an episode of acute bronchitis, the cells of the bronchial-lining tissue are irritated and the mucous membrane becomes hyperemic and edematous, diminishing bronchial mucociliary function. Consequently, the air passages become clogged by debris and irritation increases. In response, copious secretion of mucus develops, which causes the characteristic cough of bronchitis.

In the case of mycoplasmal pneumonia, bronchial irritation results from the attachment of the organism (Mycoplasma pneumoniae) to the respiratory mucosa, with eventual sloughing of affected cells. Acute bronchitis usually lasts approximately 10 days. If the inflammation extends downward to the ends of the bronchial tree, into the small bronchi (bronchioles), and then into the air sacs, bronchopneumonia results.

Chronic bronchitis is associated with excessive tracheobronchial mucus production sufficient to cause cough with expectoration for 3 or more months a year for at least 2 consecutive years. The alveolar epithelium is both the target and the initiator of inflammation in chronic bronchitis.

A predominance of neutrophils and the peribronchial distribution of fibrotic changes result from the action of interleukin 8, colony-stimulating factors, and other chemotactic and proinflammatory cytokines. Airway epithelial cells release these inflammatory mediators in response to toxic, infectious, and inflammatory stimuli, in addition to decreased release of regulatory products such as angiotensin-converting enzyme or neutral endopeptidase.

Chronic bronchitis can be categorized as simple chronic bronchitis, chronic mucopurulent bronchitis, or chronic bronchitis with obstruction. Mucoid sputum production characterizes simple chronic bronchitis. Persistent or recurrent purulent sputum production in the absence of localized suppurative disease, such as bronchiectasis, characterizes chronic mucopurulent bronchitis.

Chronic bronchitis with obstruction must be distinguished from chronic infective asthma. The differentiation is based mainly on the history of the clinical illness: patients who have chronic bronchitis with obstruction present with a long history of productive cough and a late onset of

wheezing, whereas patients who have asthma with chronic obstruction have a long history of wheezing with a late onset of productive cough.

Chronic bronchitis may result from a series of attacks of acute bronchitis, or it may evolve gradually because of heavy smoking or inhalation of air contaminated with other pollutants in the environment. When so-called smoker's cough is continual rather than occasional, the mucus-producing layer of the bronchial lining has probably thickened, narrowing the airways to the point where breathing becomes increasingly difficult. With immobilization of the cilia that sweep the air clean of foreign irritants, the bronchial passages become more vulnerable to further infection and the spread of tissue damage.

Etiology Respiratory viruses are the most common causes of acute bronchitis, and cigarette smoking is indisputably the predominant cause of chronic bronchitis.

Viral and becterial infections in acute bronchitis

The most common viruses include influenza A and B, parainfluenza, respiratory syncytial virus, and coronavirus, although an etiologic agent is identified only in a minority of cases.[1]

Acute bronchitis is usually caused by infections, such as those caused by Mycoplasma species, Chlamydia pneumoniae, Streptococcus pneumoniae, Moraxella catarrhalis, and Haemophilus influenzae, and by viruses, such as influenza, parainfluenza, adenovirus, rhinovirus, and respiratory syncytial virus. Exposure to irritants, such as pollution, chemicals, and tobacco smoke, may also cause acute bronchial irritation.

Bordetella pertussis should be considered in children who are incompletely vaccinated, though studies increasingly report this bacterium as the causative agent in adults as well.[2]

Smoking and other causes of chronic bronchitis

Cigarette smoking is indisputably the predominant cause of chronic bronchitis. Common risk factors for acute exacerbations of chronic bronchitis are advanced age and low forced expiratory volume in one second (FEV1).[3] Most (70-80%) acute exacerbations of chronic bronchitis are estimated to be due to respiratory infections.[4]

Estimates suggest that cigarette smoking accounts for 85-90% of chronic bronchitis and chronic obstructive pulmonary disease. Studies indicate that smoking pipes, cigars, and marijuana causes similar damage. Smoking impairs ciliary movement, inhibits the function of alveolar macrophages, and leads to hypertrophy and hyperplasia of mucus-secreting glands.

Smoking can also increase airway resistance via vagally mediated smooth muscle constriction. Unless some other factor can be isolated as the irritant that produces the symptoms, the first step in dealing with chronic bronchitis is for the patient to stop smoking.

Air pollution levels have been associated with increased respiratory health problems among people living in affected areas. The Air Pollution and Respiratory Health Branch of the National Center for Environmental Health directs the fight of the US Centers for Disease Control and Prevention against respiratory illness associated with air pollution.

According to the Healthy People 2000 report, each year in the United States, health costs of human exposure to outdoor air pollutants range from $40 to $50 billion, and an estimated 50,000 to 120,000 premature deaths are associated with exposure to air pollutants. In addition, the report states that those with asthma experience more than 100 million days of restricted activity, costs related to asthma exceed $4 billion, and about 4,000 people die of the condition each year.

A growing body of literature has demonstrated that specific occupational exposures are associated with the symptoms of chronic bronchitis. The list of agents includes coal, manufactured vitreous fibers, oil mist, cement, silica, silicates, osmium, vanadium, welding fumes, organic dusts, engine exhausts, fire smoke, and secondhand cigarette smoke.

EpidemiologyAccording to estimates from national interviews taken by the National Center for Health Statistics in 2006, approximately 9.5 million people, or 4% of the population, were diagnosed with chronic bronchitis. These statistics may underestimate the prevalence of chronic obstructive pulmonary disease by as much as 50%, because many patients underreport their symptoms, and their conditions remain undiagnosed.

An overdiagnosis of chronic bronchitis by patients and clinicians has also been suggested, however. The term bronchitis is often used as a common descriptor for a nonspecific and self-limited cough, thereby falsely increasing its incidence even though the patient does not meet the criteria for diagnosis.

In one study, acute bronchitis affected 44 of 1000 adults annually, and 82% of episodes occurred in fall or winter.[5] By way of comparison, 91 million cases of influenza, 66 million cases of the common cold, and 31 million cases of other acute upper respiratory tract infections occurred that year.

Acute bronchitis is common throughout the world and is one of the top 5 reasons for seeking medical care in countries that collect such data. No difference in racial distribution is reported, though bronchitis occurs more frequently in populations with a low socioeconomic status and in people who live in urban and highly industrialized areas.

In terms of gender-specific incidence, bronchitis affects males more than females. In the United States, up to two thirds of men and one fourth of women have emphysema at death. Although found in all age groups, acute bronchitis is most frequently diagnosed in children younger than 5 years, whereas chronic bronchitis is more prevalent in people older than 50 years.

Prognosis

Patients with acute bronchitis have a good prognosis. Bronchitis is almost always self-limited in individuals who are otherwise healthy, although it may result in absenteeism from work and school. Severe cases occasionally produce deterioration in patients with significant underlying cardiopulmonary disease or other comorbidities.

Complications

Complications occur in approximately 10% of patients with acute bronchitis and include the following:

Bacterial superinfection Pneumonia develops in about 5% of patients with bronchitis (incidence of subsequent

pneumonia, unaffected by antibiotic treatment) Chronic bronchitis may develop with repeated episodes of acute bronchitis Reactive airway disease can occur as a result of acute bronchitis Hemoptysis

Patient EducationPatient education is essential in the prevention and treatment of acute bronchitis. Unfortunately, health care providers usually underemphasize education. Patients should be counseled to take the following measures:

Avoid smoking and secondhand smoke Live in a clean environment Receive the influenza vaccine yearly between October and December Receive the pneumonia vaccine every 5-10 years if aged 65 years or older or with chronic

disease

For excellent patient education resources, visit eMedicine's Asthma Center.

Additionally, see eMedicine's patient education article Asthm

Bronchitis Clinical Presentation Author: Jazeela Fayyaz, DO; Chief Editor: Zab Mosenifar, MD

HistoryObtain a complete history, including information on exposure to toxic substances and smoking. Patients with chronic bronchitis are often overweight and cyanotic. Initially, cough is present in the winter months. Over the years, the cough progresses from hibernal to perennial, and mucopurulent relapses increase in frequency, the duration and severity of which increase to the point of exertional dyspnea.

Cough is the most commonly observed symptom. It begins early in the course of many acute respiratory tract infections and becomes more prominent as the disease progresses. Acute bronchitis may be indistinguishable from an upper respiratory tract infection during the first few days, though cough lasting greater than 5 days may suggest acute bronchitis.[6]

In patients with acute bronchitis, cough generally lasts from 10-20 days. Sputum production is reported in approximately half the patients in whom cough occurred. Sputum may be clear, yellow, green, or even blood-tinged. Purulent sputum is reported in 50% of persons with acute bronchitis. Changes in sputum color are due to peroxidase released by leukocytes in sputum; therefore, color alone cannot be considered indicative of bacterial infection.

Fever is a relatively unusual sign and, when accompanied by cough, suggests either influenza or pneumonia. Nausea, vomiting, and diarrhea are rare. Severe cases may cause general malaise and chest pain. With severe tracheal involvement, symptoms include burning, substernal chest pain associated with respiration, and coughing.

Dyspnea and cyanosis are not observed in adults unless the patient has underlying chronic obstructive pulmonary disease or another condition that impairs lung function.

Other symptoms of acute bronchitis include the following:

Sore throat Runny or stuffy nose Headache Muscle aches Extreme fatigue

Physical ExaminationThe physical examination findings in acute bronchitis can vary from normal-to-pharyngeal erythema, localized lymphadenopathy, and rhinorrhea to coarse rhonchi and wheezes that change in location and intensity after a deep and productive cough.

Diffuse wheezes, high-pitched continuous sounds, and the use of accessory muscles can be observed in severe cases. Occasionally, diffuse diminution of air intake or inspiratory stridor occurs; these findings indicate obstruction of a major bronchi or the trachea, which requires sequentially vigorous coughing, suctioning, and, possibly, intubation or even tracheostomy.

Sustained heave along the left sternal border indicates right ventricular hypertrophy secondary to chronic bronchitis. Clubbing on the digits and peripheral cyanosis indicate cystic fibrosis. Bullous myringitis may suggest mycoplasmal pneumonia. Conjunctivitis, adenopathy, and rhinorrhea suggest adenovirus infection.

Bronchitis Differential Diagnoses

Author: Jazeela Fayyaz, DO; Chief Editor: Zab Mosenifar, MD

Diagnostic ConsiderationsStreptococcal pharyngitis is most commonly caused by group A streptococci (45%) and anaerobes (18%), which often occur as a co-infection.

Much of the concern about diagnosing streptococcal pharyngitis is related to the complications of infection, particularly acute rheumatic fever and poststreptococcal glomerulonephritis as a late complication. Therefore, maintaining a high level of suspicion for streptococci group A in the presence of pharyngitis is advisable.

Other medical issues/problems to consider include the following:

Exercise-induced asthma Bacterial tracheitis Cough Cystic fibrosis Influenza Hyperreactive airway disease Retained foreign body Tonsillitis Occupational exposures

Differentials Alpha1-Antitrypsin Deficiency Asthma Bronchiectasis Bronchiolitis Chronic Bronchitis Chronic Obstructive Pulmonary Disease Gastroesophageal Reflux Disease Influenza Pharyngitis, Bacterial Pharyngitis, Viral Sinusitis, Acute Sinusitis, Chronic Streptococcus Group A Infections

Bronchitis Workup Author: Jazeela Fayyaz, DO; Chief Editor: Zab Mosenifar, MD

Approach Considerations Bronchitis may be suspected in patients with an acute respiratory infection with cough;

yet, because many more serious diseases of the lower respiratory tract cause cough, bronchitis must be considered a diagnosis of exclusion. A complete blood count with differential may be obtained.

Cultures and StainingObtain cultures of respiratory secretions for influenza virus, Mycoplasmapneumoniae, and Bordetella pertussis when these organisms are suspected. Culture methods and immunofluorescence tests have been developed for laboratory diagnosis of C pneumoniaeinfection.

Obtain a throat swab. Culture and gram stain of sputum is often performed, though these tests usually show no growth or only normal respiratory florae.[1]

Blood culture may be helpful if bacterial superinfection is suspected.

Procalcitonin LevelsProcalcitonin levels may be useful to distinguish bacterial infections from nonbacterial infections. Trials from 2008 and 2009 have shown that they may help guide therapy and reduce antibiotic use.[7, 8]

Sputum CytologySputum cytology may be helpful if the cough is persistent.

Chest RadiographyChest radiography should be performed in those patients whose physical examination findings suggest pneumonia. Elderly patients may have no signs of pneumonia; therefore, chest radiography may be warranted in these patients, even without other clinical signs of infection.

BronchoscopyBronchoscopy may be needed to exclude foreign body aspiration, tuberculosis, tumors, and other chronic diseases of the tracheobronchial tree and lungs.

Influenza TestingInfluenza tests may be useful. Additional serologic tests, such as that for atypical pneumonia, are not indicated.

SpirometrySpirometry may be useful because patients with acute bronchitis often have significant bronchospasm, with a large reduction in forced expiratory volume in one second (FEV1). This generally resolves over 4-6 weeks.

LaryngoscopyLaryngoscopy can exclude epiglottitis.

Histologic Findings Goblet cell hyperplasia, mucosal and submucosal inflammatory cells, edema, peribronchial fibrosis, intraluminal mucous plugs, and increased smooth muscle are characteristic findings in small airways in chronic obstructive lung disease.

Bronchitis Treatment & Management Author: Jazeela Fayyaz, DO; Chief Editor: Zab Mosenifar, MD more...

Medical CareTherapy is generally focused on alleviation of symptoms.Toward this goal, a doctor may prescribe a combination of medications that open obstructed bronchial airways and thin obstructive mucus so that it can be coughed up more easily. Care for acute bronchitis is primarily supportive and should ensure that the patient is oxygenating adequately. Bed rest is recommended.

The most effective means for controlling cough and sputum production in patients with chronic bronchitis is the avoidance of environmental irritants, especially cigarette smoke.

To see complete information on Pediatric Bronchitis, please go to the main article by clicking here.

Symptomatic TreatmentBased on 2006 American College of Chest Physicians (ACCP) guidelines,[9, 10] central cough suppressants such as codeine and dextromethorphan are recommended for short-term symptomatic relief of coughing in patients with acute and chronic bronchitis.[11]

Also based on 2006 ACCP guidelines, therapy with short-acting beta-agonists ipratropium bromide and theophylline can be used to control symptoms such as bronchospasm, dyspnea, and chronic cough in stable patients with chronic bronchitis. For this group, treatment with a long-acting beta-agonist, when coupled with an inhaled corticosteroid, can be offered to control chronic cough.

For details on these guidelines, see Chronic cough due to chronic bronchitis: ACCP evidence-based clinical practice guidelines and Chronic cough due to acute bronchitis: ACCP evidence-based clinical practice guidelines.

For patients with an acute exacerbation of chronic bronchitis, therapy with short-acting agonists or anticholinergic bronchodilators should be administered during the acute exacerbation. In addition, a short course of systemic corticosteroid therapy may be given and has been proven to be effective.

In acute bronchitis, treatment with beta2-agonist bronchodilators may be useful in patients who have associated wheezing with cough and underlying lung disease. Little evidence indicates that the routine use of beta2-agonists is otherwise helpful in adults with acute cough.[12]

Nonsteroidal anti-inflammatory drugs are helpful in treating constitutional symptoms of acute bronchitis, including mild-to-moderate pain. Albuterol and guaifenesin products treat cough, dyspnea, and wheezing.

In patients with chronic bronchitis or chronic obstructive pulmonary disease (COPD), treatment with mucolytics has been associated with a small reduction in acute exacerbations and a reduction in the total number of days of disability. This benefit may be greater in individuals who have frequent or prolonged exacerbations.[13] Mucolytics should be considered in patients with moderate-to-severe COPD, especially in the winter months.[3]

Antibiotic TherapyAmong otherwise healthy individuals, antibiotics have not demonstrated any consistent benefit in the symptomatology or natural history of acute bronchitis.[14, 15] Most reports have shown that 65-80% of patients with acute bronchitis receive an antibiotic despite evidence indicating that, with few exceptions, they are ineffective. An exception is with cases of acute bronchitis caused by suspected or confirmed pertussis infection.

The most recent recommendations on whether to treat patients with acute bronchitis with antibiotics are from the National Institute for Health and Clinical Excellence in the United Kingdom. They recommend not treating acute bronchitis with antibiotics unless a risk of serious complications exists because of comorbid conditions. Antibiotics, however, are recommended in patients older than 65 years with acute cough if they have had a hospitalization in the past year, have diabetes mellitus or congestive heart failure, or are on steroids.[16]

In patients with acute exacerbations of chronic bronchitis, the use of antibiotics is recommended. Trials have shown that antibiotics improve clinical outcomes in such cases, including a reduction in mortality.[17, 18]

A meta-analysis found no difference in treatment success for acute exacerbations of chronic bronchitis with macrolides, quinolones, or amoxicillin/clavulanate.[19] Another meta-analysis comparing the effectiveness of semisynthetic penicillins to trimethoprim-based regimens found no difference in treatment success or toxicity.[20] These findings support earlier studies that have shown antibiotics to be useful in exacerbations of chronic bronchitis, regardless of the agent used.

In addition, a short course of antibiotics (5 d) is as effective as the traditional longer treatments (>5 d) in these patients.[21] Patients with severe exacerbations and those with more severe airflow obstruction at baseline are the most likely to benefit. In stable patients with chronic bronchitis, long-term prophylactic therapy with antibiotics is not indicated.

Influenza VaccinationsThe influenza vaccine may reduce the incidence of upper respiratory tract infections and, subsequently, reduce the incidence of acute bacterial bronchitis. The influenza vaccine may be less effective in preventing illness than it is in preventing serious complications and death.[22]

In the United States, the flu season usually occurs from approximately October to April. The Centers for Disease Control and Prevention (CDC) provisional recommendations for the 2010-2011 influenza season recommend vaccination for all people aged 6 months and older. The 2010–2011 vaccine will be a trivalent vaccine, which will cover H1N1. In certain situations, such as in nursing homes, consider administration of oseltamivir or zanamivir when an index case is found until the vaccine has had a chance to take effect. Pneumococcal vaccination is recommended in patients with chronic bronchitis.

ZincSeveral studies have shown conflicting results on the use of zinc as an adjunct treatment against influenza A. Most studies demonstrated favorable results, but participants complained of a bad taste and significant nausea.

On June 16, 2009, the US Food and Drug Administration (FDA) issued a public health advisory and notified consumers and health care providers to discontinue use of intranasal zinc products. The intranasal zinc products (Zicam Nasal Gel/Nasal Swab products by Matrixx Initiatives) are herbal cold remedies that claim to reduce the duration and severity of cold symptoms and are sold without a prescription. The FDA received more than 130 reports of anosmia (inability to detect odors) associated with intranasal zinc. Many of the reports described the loss of the sense of smell with the first dose.[23]

Consultations

Primary care providers can usually treat acute bronchitis unless severe complications occur or the patient has underlying pulmonary disease or immunodeficiency. Pulmonary medicine specialists and infectious disease specialists also may need to be consulted.

Long-Term MonitoringRoutine follow-up care is usually not necessary. If symptoms worsen (eg, shortness of breath, high fever, vomiting, persistent cough), consider an alternative diagnosis. If symptoms recur (> 3 episodes/y), further investigation is recommended. If symptoms persist beyond 1 month, reassess patient for other causes of cough.

Medication SummaryTherapy for patients with acute bronchitis is generally aimed toward alleviation of symptoms and includes the use of analgesics, antipyretics, antitussives, and expectorants.

Among otherwise healthy individuals, antibiotics have not demonstrated consistent benefit in the symptomatology or natural history of acute bronchitis.[9, 24] Nonetheless, surveys from Europe, Australia, and the United States show that 80% of patients with acute bronchitis receive antibiotics.

Antibiotic overuse contributes to the emergence of drug-resistant organisms. Cognizant of this, the Centers for Disease Control and Prevention recently collaborated with numerous medical societies to publish a series of articles on the judicious use of antibiotics for several common conditions, including bronchitis, and have recommended against routine antibiotic use in uncomplicated bronchitis.

Patients are up to 4 times more likely to expect antibiotics for the diagnosis of bronchitis than for a chest cold. Therefore, limiting use of the diagnosis of bronchitis may make reduction of antibiotic use more acceptable to patients.

Reviews have also noted that antibiotic use in smokers without chronic obstructive pulmonary disease is no more effective than use in nonsmokers.[25]

Antimicrobials

Class Summary

Studies have focused on healthy individuals (patients with asthma excluded) or patients with chronic obstructive pulmonary disease (COPD). Antimicrobials appear to offer a small benefit when treating patients with COPD, and trimethoprim-sulfamethoxazole remains a good and inexpensive choice. Amoxicillin and doxycycline are also good alternatives. Therefore, extending antimicrobial use to patients with asthma and others with limited cardiopulmonary reserve may be reasonable.

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Amoxicillin and clavulanate (Augmentin)

This agent inhibits bacterial cell wall synthesis by binding to penicillin-binding proteins. The addition of clavulanate inhibits beta-lactamase–producing bacteria.

It is a good alternative antibiotic for patients allergic to or intolerant of the macrolide class. It is usually well tolerated and provides good coverage of most infectious agents, but it is not effective against Mycoplasma and Legionella species. The half-life of the oral dosage is 1-1.3 hours. It has good tissue penetration but does not enter the cerebrospinal fluid.

For children older than 3 months, base the dosing protocol on amoxicillin content. Because of different amoxicillin/clavulanic acid ratios in the 250-mg tab (250/125) vs the 250-mg chewable tab (250/62.5), do not use the 250-mg tab until the child weighs more than 40 kg.

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Erythromycin (E.E.S., E-Mycin, Ery-Tab)

Erythromycin inhibits bacterial growth, possibly by blocking dissociation of peptidyl tRNA from ribosomes, causing RNA-dependent protein synthesis to arrest. It is indicated for staphylococcal, streptococcal, chlamydial, and mycoplasmal infections.

Azithromycin (Zithromax)

Azithromycin acts by binding to the 50S ribosomal subunit of susceptible microorganisms and blocks dissociation of peptidyl tRNA from ribosomes, causing RNA-dependent protein synthesis to arrest. Nucleic acid synthesis is not affected.

It concentrates in phagocytes and fibroblasts, as demonstrated by in vitro incubation techniques. In vivo studies suggest that the concentration in phagocytes may contribute to drug distribution to inflamed tissues. Azithromycin treats mild-to-moderate microbial infections.

Tetracycline (Sumycin)

Tetracycline may be an option outside the United States. It treats gram-positive and gram-negative organisms, as well as mycoplasmal, chlamydial, and rickettsial infections. This agent

inhibits bacterial protein synthesis by binding with the 30S and, possibly, the 50S ribosomal subunit(s). It is less effective than erythromycin.

Cefditoren (Spectracef)

Cefditoren is a semisynthetic cephalosporin administered as a prodrug. It is hydrolyzed by esterases during absorption and is distributed in circulating blood as active cefditoren.

Bactericidal activity results from inhibition of cell wall synthesis via an affinity for penicillin-binding proteins. No dose adjustment is necessary for mild renal impairment (CrCl 50-80 mL/min/1.73 m2) or mild-to-moderate hepatic impairment. It is indicated for acute exacerbation of chronic bronchitis caused by susceptible strains of S pyogenes.

The 400-mg dose is indicated for AECB caused by susceptible strains of H influenzae, H parainfluenzae, S pneumoniae (penicillin-susceptible strains only), or M catarrhalis.

Trimethoprim-sulfamethoxazole (Bactrim DS, Septra)

Trimethoprim-sulfamethoxazole inhibits bacterial synthesis of dihydrofolic acid by competing with para-aminobenzoic acid, resulting in inhibition of bacterial growth. Antibacterial activity of trimethoprim-sulfamethoxazole includes common urinary tract pathogens, except Pseudomonas aeruginosa. As with tetracycline, it has in vitro activity against B pertussis. It is not useful in mycoplasmal infections.

Amoxicillin (Biomox, Trimox, Amoxil)

Amoxicillin interferes with synthesis of cell wall mucopeptides during active multiplication, resulting in bactericidal activity against susceptible bacteria.

Levofloxacin (Levaquin)

Levofloxacin has a bacteriocidal property by inhibiting the DNA gyrase and, consequently, cell growth.

Clarithromycin (Biaxin)

Clarithromycin is a semisynthetic macrolide antibiotic that reversibly binds to the P site of the 50S ribosomal subunit of susceptible organisms and may inhibit RNA-dependent protein synthesis by stimulating dissociation of peptidyl t-RNA from ribosomes, causing bacterial growth inhibition.

Doxycycline (Bio-Tab, Doryx, Vibramycin)

Doxycycline is a broad-spectrum, synthetically derived bacteriostatic antibiotic in the tetracycline class. It is almost completely absorbed, concentrates in bile, and is excreted in urine and feces as a biologically active metabolite in high concentrations.

It inhibits protein synthesis and, thus, bacterial growth by binding to 30S and possibly 50S ribosomal subunits of susceptible bacteria. It may block dissociation of peptidyl t-RNA from ribosomes, causing RNA-dependent protein synthesis to arrest.

Antitussives/expectorants

Class Summary

Sparse data attest to the efficacy of expectorants outside the test tube.

Guaifenesin with dextromethorphan (Humibid DM, Robitussin DM)

This agent treats minor cough resulting from bronchial and throat irritation.

Codeine/guaifenesin (Robitussin AC)

The prototype antitussive, codeine, has been used successfully in some chronic cough and induced-cough models, but scant clinical data exist for upper respiratory tract infections.

Bronchodilators

Class Summary

Studies (although limited) have shown an advantage to using bronchodilators and possible superiority to antibiotics for relieving bronchitis symptoms.

Albuterol (Proventil, Ventolin)

Albuterol relaxes bronchial smooth muscle by action on beta2-receptors with little effect on cardiac muscle contractility.

Metaproterenol sulfate

Metaproterenol is a beta agonist for bronchospasms that relaxes bronchial smooth muscle by action on beta2 receptors with little effect on cardiac muscle contractility.

Theophylline (Theo-24, Uniphyl)

Theophylline is used to control symptoms such as bronchospasm, dyspnea, and chronic cough in stable patients with chronic bronchitis. It potentiates exogenous catecholamines and stimulates endogenous catecholamine release and diaphragmatic muscular relaxation, which, in turn, stimulates bronchodilation.

Ipratropium

Ipratropium is an anticholinergic bronchodilator that is often used to control symptoms such as bronchospasm, dyspnea, and chronic cough in stable patients with chronic bronchitis.

Corticosteroids, Systemic

Class Summary

For patients with an acute exacerbation of chronic bronchitis, a short course of systemic corticosteroid therapy may be given and has been proven to be effective.

Prednisolone (Pediapred, Orapred)

Prednisolone works by decreasing inflammation by suppressing migration of polymorphonuclear leukocytes and reducing capillary permeability.

Prednisone (Sterapred)

Prednisone may decrease inflammation by reversing increased capillary permeability and suppressing polymorphonuclear leukocyte activity. Prednisone stabilizes lysosomal membranes and suppresses lymphocytes and antibody production.

orticosteroids, Inhaled

Class Summary

Corticosteroids are the most potent anti-inflammatory agents. Inhaled forms are topically active, poorly absorbed, and least likely to cause adverse effects. In patients who are stable with chronic bronchitis, treatment with a long-acting beta-agonist coupled with an inhaled corticosteroid may offer relief of chronic cough.

Beclomethasone (Qvar)

Beclomethasone inhibits bronchoconstriction mechanisms, causes direct smooth muscle relaxation, and may decrease the number and activity of inflammatory cells, which, in turn, decrease airway hyperresponsiveness. It is available in a metered-dose inhaler (MDI) that delivers 40 or 80 mcg/actuation.

Fluticasone (Flovent HFA, Flovent Diskus)

Fluticasone has extremely potent vasoconstrictive and anti-inflammatory activity. It is available in an MDI (44-mcg, 110-mcg, or 220-mcg per actuation) and Diskus powder for inhalation (50-mcg, 100-mcg, or 250-mcg per actuation).

Budesonide (Pulmicort Flexhaler, Pulmicort Respules)

Budesonide reduces inflammation in airways by inhibiting multiple types of inflammatory cells and decreasing production of cytokines and other mediators involved in the asthmatic response. It is available as Flexhaler powder for inhalation (90 mcg/actuation [delivers approximately 80 mcg/actuation]) and Respules suspension for inhalation.

Antiviral Agents

Class Summary

Influenza vaccinations offer greater protection for the appropriate populations because they offer coverage for influenza A and B. The Centers for Disease Control and Prevention (CDC) provisional recommendations for the 2010-2011 influenza season recommend expanded vaccination; all people aged 6 months and older should receive annual influenza vaccine.[26] The 2010-2011 vaccine will be a trivalent vaccine.

Influenza A viruses, including the 2 subtypes H1N1 and H3N2, and influenza B viruses currently circulate worldwide, but the prevalence of each can vary among communities and within a single community over the course of an influenza season.

In the 2009-2010 flu season, approximately 99% of typed influenza viruses were H1N1. In the United States, 4 prescription antiviral medications (ie, oseltamivir, zanamivir, amantadine, rimantadine) are approved for treatment and chemoprophylaxis of influenza.

The vast majority of the 2009-2010 influenza was susceptible to oseltamivir and zanamivir but resistant to the adamantanes (amantadine, rimantadine). In addition, the FDA issued an emergency use authorization for a third neuraminidase inhibitor, peramivir, for the treatment of hospitalized patients with H1N1 influenza who have potentially life-threatening suspected or laboratory-confirmed infection. Peramivir IV is available through the CDC upon request of a licensed physician.[23]

Complete recommendations are available in a CDC Health Advisory.

Zanamivir (Relenza)

Zanamivir is an inhibitor of neuraminidase, which is a glycoprotein on the surface of the influenza virus that destroys the infected cell's receptor for viral hemagglutinin. By inhibiting viral neuraminidase, release of viruses from infected cells and viral spread are decreased. It is effective against both influenza A and B and is inhaled through Diskhaler oral inhalation device. Circular foil disks containing 5-mg blisters of drug are inserted into the supplied inhalation device.

Rimantadine (Flumadine)

Rimantadine inhibits viral replication of influenza A virus H1N1, H2N2, and H3N2 and prevents viral penetration into a host by inhibiting uncoating of influenza A. NOTE: Because of resistance, it is not recommended by the CDC as of the 2005-2006 influenza season. Laboratory testing by the CDC on the predominant strain of influenza (H3N2) currently circulating in the United States shows that it is resistant to these drugs.

Oseltamivir (Tamiflu)

Oseltamivir inhibits neuraminidase, which is a glycoprotein on the surface of influenza virus that destroys an infected cell's receptor for viral hemagglutinin. By inhibiting viral neuraminidase, this agent decreases release of viruses from infected cells and thus viral spread. It is effective in treating influenza A or B. Start within 40 hours of symptom onset. It is available as a capsule and oral suspension.

Peramivir (Rapiacta)

Peramivir is an investigational neuraminidase inhibitor. Emergency-use authorization has been issued by the FDA for use of peramivir in hospitalized adult and pediatric patients with suspected or laboratory-confirmed 2009 H1N1 influenza unresponsive to oseltamivir or zanamivir, in patients unable to take PO or inhaled drugs (or delivery route not dependable or feasible), or in other patients determined by clinician. To request peramivir, see the information at www.cdc.gov/h1n1flu/eua or call (800) CDC-INFO (232-4636).

Analgesics/antipyretics

Class Summary

Analgesics and antipyretics are often helpful in relieving the associated lethargy, malaise, and fever associated with illness.

Ibuprofen (Ibuprin, Advil, Motrin)

Ibuprofen is usually DOC for treatment of mild to moderate pain, if no contraindications exist.

Acetaminophen (Tylenol, Panadol, Aspirin-Free Anacin)

Acetaminophen is DOC for treatment of pain in patients who have documented hypersensitivity to aspirin or NSAIDs, who have upper gastrointestinal disease, or who are taking oral anticoagulants.

http://emedicine.medscape.com/article/297108-medication#8 Retrieved April 18, 2011

Bronchitis (acute)

Definition

Acute bronchitis is a transient inflammation of the trachea and major bronchi. Clinically, it is diagnosed on the basis of cough and occasionally sputum, dyspnoea, and wheeze. This review is limited to episodes of acute bronchitis in people (smokers and non-smokers) with no pre-existing respiratory disease (such as a pre-existing diagnosis of asthma or chronic bronchitis, evidence of fixed airflow obstruction, or both) and excluding those with clinical or radiographic evidence of pneumonia. However, the reliance on a clinical definition for acute bronchitis implies that people with conditions such as transient/mild asthma or mild chronic obstructive pulmonary disease may have been recruited in some of the reported studies

Incidence / Prevalence

Acute bronchitis affects 44/1000 adults (age over 16 years) each year in the UK, with 82% of episodes occurring in autumn or winter. [1] One survey found that acute bronchitis was the fifth most common reason for people of any age to present to a general practitioner in Australia. [2]

Aetiology / Risk factors

Infection is believed to be the trigger for acute bronchitis. However, pathogens have been identified in less than 55% of people. [1] Community studies that attempted to isolate pathogens from the sputum of people with acute bronchitis found viruses in 8% to 23% of people, typical bacteria ( Streptococcus pneumoniae, Haemophilus influenzae, Moraxella catarrhalis) in 45%, and atypical bacteria ( Mycobacterium pneumoniae, Chlamydia pneumoniae, Bordetella pertussis) in 0% to 25%. [1] [3] [4] It is unclear whether smoking affects the risk for developing acute bronchitis.

Prognosis

Acute bronchitis is regarded as a mild, self-limiting illness, but there are limited data on prognosis and rates of complications, such as chronic cough or progression to chronic bronchitis or pneumonia. One prospective longitudinal study reviewed 653 previously well adults who presented to suburban general practices over a 12-month period with symptoms of acute lower respiratory tract infection. [1] It found that, within the first month of the illness, 20% of people re-presented to their general practitioner with persistent or recurrent symptoms, mostly persistent cough. The no-treatment control group of one RCT (212 people; about 16% took antibiotics outside of the study protocol) found that participants had at least a slight problem with cough for a mean of 11.4 days, with “moderately bad” cough lasting for a mean of 5.7 days. Another prospective study of 138 previously well adults found that 34% had symptoms consistent with either chronic bronchitis or asthma 3 years after initial presentation with acute bronchitis. [5] It is also unclear whether acute bronchitis plays a causal role in the progression to chronic bronchitis,

or is simply a marker of predisposition to chronic lung disease. Although smoking has been identified as the most important risk factor for chronic bronchitis, [6] [7] it is unclear whether the inflammatory effects of cigarette smoke and infection causing acute bronchitis have additive effects in leading to chronic inflammatory airway changes. In children, exposure to parental environmental tobacco smoke is associated with an increase in risk for community lower respiratory tract infection in children aged 0 to 2 years, and an increase in symptoms of cough and phlegm in those aged 5 to 16 years. [8]

Aims of intervention

To improve symptoms associated with acute bronchitis; to reduce complications, with minimal adverse effects.

Outcomes

Symptom severity: duration of symptoms, particularly cough, sputum production, and fever; limitation of activities; clinical improvement.

Complications of acute bronchitis: especially chronic cough, pneumonia, and chronic bronchitis. Quality of life. Adverse effects.

Methods

Clinical Evidence search and appraisal September 2007. The following databases were used to identify studies for this review: Medline 1966 to September 2007, Embase 1980 to September 2007, and The Cochrane Database of Systematic Reviews 2007, Issue 2. Additional searches were carried out using the following websites: NHS Centre for Reviews and Dissemination (CRD), Database of Abstracts of Reviews of Effects (DARE), Health Technology Assessment (HTA), Turning Research into Practice (TRIP), and NICE. Abstracts of the studies retrieved were assessed independently by two information specialists using predetermined criteria to identify relevant studies. We included people of any age or sex with acute bronchitis. We excluded trials conducted in people who had chronic respiratory disease or other acute respiratory diseases. We excluded non-systematic reviews, non-randomised trials, and RCTs that were not double blinded, comprised fewer than 20 people, or were of less than 4 days' treatment duration or had less than 2 weeks' duration of follow-up. We did not exclude studies based on loss to follow-up. We excluded all studies described as “open”, “open label”, or “single blinded”. Where systematic reviews were being regularly updated, we only included the most updated version of the review, and made note of previous versions if the conclusions had altered. Where there was more than one systematic review about an option, both reviews were examined and their results commented on. Consideration was given to the quality of the review in terms of its methods of inclusion, its assessment of the literature (published and non-published), and any potential conflicts of interest. If one systematic review was felt to be outdated and a more recent version existed, or new RCTs had emerged that were felt to alter the conclusions of the review, then this was reported and a decision made to include or exclude the review. A regular

surveillance protocol is used to capture harms alerts from organisations such as the FDA and the UK Medicines and Healthcare products Regulatory Agency (MHRA), which are continually added to the chapter as required. We have performed a GRADE evaluation of the quality of evidence for interventions included in this review ( see table). The categorisation of the quality of the evidence (high, moderate, low, or very low) reflects the quality of evidence available for our chosen outcomes in our defined populations of interest. These categorisations are not necessarily a reflection of the overall methodological quality of any individual study, because the Clinical Evidence population and outcome of choice may represent only a small subset of the total outcomes reported, and population included, in any individual trial. For further details of how we perform the GRADE evaluation and the scoring system we use, please see our website (www.clinicalevidence.com).

References

1. Macfarlane J, Holmes W, Gard P, et al. Prospective study of the incidence, aetiology and outcome of adult lower respiratory tract illness in the community. Thorax 2001;56:109–114. [PubMed]

2. Meza RA. The management of acute bronchitis in general practice results from the Australian morbidity and treatment survey. Aust Fam Physician 1994;23:1550–1553. [PubMed]

3. Boldy DAR, Skidmore SJ, Ayres JG. Acute bronchitis in the community: clinical features, infective factors, changes in pulmonary function and bronchial reactivity to histamine. Respir Med 1990;84:377–385. [PubMed]

4. Grayston JT, Aldous MB, Easton A, et al. Evidence that Chlamydia pneumoniae causes pneumonia and bronchitis. J Infect Dis 1993;168:1231–1235. [PubMed]

5. Jonsson JS, Gislason T, Gislason D, et al. Acute bronchitis and clinical outcome three years later: prospective cohort study. BMJ 1998;317:1433. [PubMed]

6. Whittemore AS, Perlin SA, DiCiccio Y. Chronic obstructive pulmonary disease in lifelong nonsmokers: results from NHANES. Am J Public Health 1995;85:702–706. [PubMed]

7. Brunekreef B, Fischer P, Remijn B, et al. Indoor air pollution and its effects on pulmonary function of adult non-smoking women: III. Passive smoking and pulmonary function. Int J Epidemiol 1985;14:227–230. [PubMed]

8. Cook DG, Strachan DP. Summary of effects of parental smoking on the respiratory health of children and implications for research. Thorax 1999;54:357–366. [PubMed]

ACUTE BRONCHITIS

Acute bronchitis is marked by a sudden cough, productive or nonproductive, that has persisted for less than three weeks with no evidence of pneumonia, common cold, acute asthma, or exacerbation of chronic obstructive pulmonary disease. In most otherwise healthy patients with an acute cough, the absence of tachycardia, tachypnea, fever, and abnormal findings on chest examination indicates that pneumonia isn't likely. Note that the presence of purulent sputum does not distinguish acute bronchitis from pneumonia.53

Acute bronchitis has been linked to several bacteria and viruses as well as noninfectious etiologies. Known viral etiologic agents include influenza viruses, picornavirus (including rhinovirus), respiratory syncytial virus, among others.54, 55 Known bacterial etiologic agents include S. pneumoniae, Haemophilus influenzae, Moraxella catarrhalis, and Bordetella pertussis.55-57 Atypical etiologic agents include Chlamydia pneumoniae (also known as Chlamydophila pneumoniae) and Mycoplasma pneumoniae.55,57 Regardless of etiology, most patients recover from acute bronchitis without antibiotics57; therefore, otherwise healthy adults and children with bronchitis should not routinely be treated with antibiotics.58, 59

For a variety of reasons, including improvements in diagnosis, increased reporting of the disease, and the fact that the vaccine's effectiveness diminishes over time, rates of B. pertussis infection (whooping cough) are on the rise, and the disease is estimated to be responsible for 20% of prolonged cough illnesses (those lasting longer than three weeks) in adults and adolescents.60 Current guidelines recommend that people who experience a cough for two or more weeks with symptoms typical of pertussis (for example, paroxysmal coughing, posttussive vomiting, an inspiratory whooping sound, or some combination of these) and no other likely etiology for the cough (such as asthma) should be evaluated for B. pertussis infection.61 Patients with suspected or confirmed B. pertussis infection should be treated with a macrolide antibiotic (for example, azithromycin, clarithromycin, or erythromycin).56 A macrolide antibiotic should also be administered to close contacts of a person with pertussis, if there are no contraindications. All cases of confirmed pertussis should be reported to officials at the applicable state health department, who will then assist with tracing and identifying those who should receive prophylactic treatment.62

Management of uncomplicated acute bronchitis should focus on reassuring patients and their caregivers that bronchitis is usually a viral illness that resolves in two weeks without treatment. Patients should also be advised to get an evaluation by a clinician for a persistent cough (one that lasts longer than two weeks) or a cough accompanied by extreme lethargy, anorexia, difficulty breathing, or cyanosis. Unfortunately, research efforts to date have yet to identify the best way to decrease cough. Inhaled and oral β2-receptor agonists (such as albuterol [Proventil and others]) may be of some help in cases of acute bronchitis when airflow obstruction and wheezing are present, but these medications are not recommended for routine use in acute bronchitis.53 The use of antitussive agents, such as dextromethorphan and codeine, in patients with acute bronchitis has not been thoroughly studied. Mixed results have been achieved with these medications in patients experiencing cough from the common cold.53 Until further data are available, a short trial of antitussive agents for cough associated with acute bronchitis is probably a reasonable treatment option. But expectorants and mucolytic agents (such as guaifenesin) have been shown

to be of no benefit to patients with cough from acute bronchitis and are not recommended for routine use.53

http://journals.lww.com/ajnonline/Fulltext/2008/06000/Acute_Respiratory_Infections_and_Antimicrobial.24.aspx

Socioeconomic status, asthma and chronic bronchitis in a large community-based study AbstractThe present study investigated the relationship between socioeconomic status, using measures of occupational class and education level, and the prevalence and incidence of asthma (with and without atopy) and chronic bronchitis using data from the European Community Respiratory Health Survey (ECRHS).

Asthma and chronic bronchitis were studied prospectively within the ECRHS (n = 9,023). Incidence analyses comprised subjects with no history of asthma or bronchitis at baseline. Asthma symptoms were also assessed as a continuous score.

Bronchitis risk was associated with low educational level (prevalence odds ratio (POR) 1.9; 95% confidence interval (CI) 1.4–2.8) and occupational class (1.8; 1.2–2.7). Incident bronchitis also increased with low educational level (risk ratio (RR) 2.8; 95%CI 1.5–5.4). Prevalent and incident asthma with no atopy were associated with low educational level. Subjects in the low occupational class (incident risk ratio (IRR) 1.4; 95%CI 1.2–1.7) and education group (IRR 1.3; 95% CI 1.1–1.6) had higher mean asthma scores than those in higher socioeconomic groups.

Lower educational level was associated with increased risk of prevalent and incident chronic bronchitis and asthma with no atopy. Lower socioeconomic groups tended to have a higher prevalence and incidence of asthma, particularly higher mean asthma scores. Adjustment for variables associated with asthma and bronchitis explained little of the observed health differences by socioeconomic status.

The relationships between socioeconomic status (SES) and asthma prevalence and incidence are not well understood. Previous studies in adults have reported no association 1, 2, while others have reported an increased asthma prevalence with lower SES 3, 4. Some of the inconsistencies may be due to a lack of standardisation between studies, particularly with regard to definitions and measurement of asthma and SES. Not only are there difficulties in defining asthma 5, but in addition the relationship between asthma prevalence and incidence is not easy to disentangle 6,

7. Furthermore, as with other chronic conditions such as diabetes and coronary heart disease, asthma may have shifted from being more prevalent among the affluent to becoming a condition more strongly associated with poverty in recent years 8, 9. Additionally, differing patterns of SES have been observed in the prevalence of atopic and nonatopic asthma 10, 11.

In general, little is known about the pathways and mechanisms by which SES affects respiratory disease in adults. A number of risk factors that may be involved in the interrelationship between SES and asthma and chronic bronchitis have been identified: 1) smoking 12; 2) exposure to environmental tobacco smoke (ETS) 13; 3) mould or mildew in the home 14; 4) allergen sensitisation 15; and 5) obesity 16. Some of these factors, e.g. tobacco smoke 12, show a stronger association with chronic bronchitis than with asthma.

The European Community Respiratory Health Survey (ECRHS) previously examined the relationship between SES and asthma prevalence 3. An increased asthma prevalence amongst lower socioeconomic groups was observed at the individual level, with education also being a determinant of asthma risk at the centre level. The ECRHS II study was undertaken 10 yrs later to assess changes over time in the prevalence and incidence of asthma and associated respiratory symptoms. The objective of the current analysis was to investigate the relationship between SES, based on measures of occupational class and educational level, with the prevalence and incidence of asthma (with and without atopy) and chronic bronchitis.

METHODS

Study population

The ECRHS sampling framework includes a random and asymptomatic sample. Details have been described elsewhere 17, 18. ECRHS I subjects were 20–44 yrs of age and randomly selected from the general population in centres from throughout Europe, the USA, Australia and New Zealand during 1991–1993. All participants completing ECRHS I were invited to take part in a follow-up study, ECRHS II, during 1999–2001. The study population for the current analyses comprises those subjects who participated in both surveys and had occupational information collected in ECRHS II (28 centres from 13 countries).

SES was based on the subject's occupation and education level. Occupational class was derived from the longest-held job during the follow-up period between ECRHS I and II. Categories were based on the major group classification, using the first digit of the International Standard Classification of Occupations (ISCO) 19. If a subject held multiple jobs for the same time duration during the follow-up period, then the lower ISCO category (i.e. higher skill level) was used. The categories were: I for managers and professionals (nonmanual) of major groups 1 and 2; II for technicians and associate professionals of major group 3; III for other nonmanual workers of major groups 4 and 5; IV for skilled manual workers of major groups 6 and 7; V for semi-skilled or unskilled manual workers of major groups 8 and 9; and VI for unclassifiable or unknown. Occupational class group VI comprised any individual not occupationally active during follow-up or who could not be assigned an ISCO code. Each occupational class is presented in table 1⇓ describing the study population but, thereafter, classes IV and V were combined for the analyses.

Table 1—

Characteristics of participants in the European Community Respiratory Health Survey II(1999–2001)#

Educational level was based on age of the subject at completion of full-time study. To enable comparability of education level between countries, country-specific tertiles were constructed to provide a relative educational level measure, therefore, the cut-points for each country are different. Tertiles of education level were categorised as high (reference category), medium and low.

The prevalence analyses included 9,023 subjects (response rate 59%; fig. 1⇓). Current asthma was defined as at least one of the following factors in the previous 12 months: 1) having an asthma attack; 2) woken by an attack of shortness of breath; or 3) currently using asthma medication 17. Atopic status was determined by blood sample measurement of immunoglobulin (Ig)E and defined as specific sensitisation to at least one of the following common allergens: Dermatophagoides pteronyssinus, Cladosporium herbarum, cat or Timothy-grass (specific IgE >0.35 KU·L−1) 3. A total of 169 subjects who did not have complete information on asthma status and 1,889 subjects with missing information on atopic status were excluded, leaving 6,965 subjects in the asthma prevalence analyses.

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Fig. 1—

Selection of the study population for the European Community Respiratory Health Survey (ECRHS) II socioeconomic status, asthma and chronic bronchitis study. SOB: shortness of breath.

Prevalent bronchitis was defined as the presence of both cough and phlegm on most days for ≥3 months during the previous year 20. Discordant responses (n = 871), i.e. subjects reporting at ECRHS II either only chronic cough or only chronic phlegm but not both, were excluded. No subjects reported both chronic cough and chronic phlegm in Tartu (Estonia), so this centre was excluded from the analysis (n = 259), leaving 7,915 subjects.

The cumulative incidence of asthma was defined as the proportion of subjects without asthma symptoms at ECRHS I who subsequently reported asthma symptoms at ECRHS II. In total, 1,743 subjects were excluded after reporting any of the following symptoms: current asthma and/or shortness of breath or wheeze (with no cold) at the time of ECRHS I. A further 1,604 subjects were excluded due to missing data on atopic status, leaving 5,645 subjects in the

incident asthma analyses. Both the asthma prevalence and incidence analyses were stratified according to atopic status.

The cumulative incidence ratio for chronic bronchitis was calculated based on the proportion of subjects having neither cough nor phlegm at ECRHS I who then reported having both symptoms at ECRHS II. A total of 1,796 subjects were excluded who responded “yes” to having cough or phlegm at ECRHS I. Subjects with discordant responses to the questions on cough and phlegm (n = 470) were excluded, in addition to respondents from Tartu (n = 178) and Bordeaux, France (n = 124), where there were no incident cases of bronchitis reported for the follow-up period, leaving 6,455 participants.

In the incidence analyses, responses to six questions on asthma symptoms were combined into an asthma score ranging 0–6 7. The items were: 1) breathless while wheezing in the previous 12 months; 2) waking with a feeling of chest tightness in the previous 12 months; 3) attack of shortness of breath at rest in the previous 12 months; 4) attack of shortness of breath after exercise in the previous 12 months; 5) waking by attack of shortness of breath in the previous 12 months; and 6) the presence of asthma ever. These analyses were conducted in those subjects (n = 5,924) reporting none of the six asthma symptoms at baseline.

Study variables

All subjects provided information on asthma, bronchitis, respiratory symptoms, allergic conditions, lifestyle and environment via an interviewer-administered questionnaire previously validated in ECRHS I 17. Outcome measures were: 1) prevalence of asthma (with and without atopy) and chronic bronchitis at ECRHS II; 2) cumulative incidence of asthma (with and without atopy) between ECRHS I and II; 3) cumulative incidence of chronic bronchitis between ECRHS I and II; and 4) asthma score at ECRHS II.

Objective measurements of the subject's height and weight were obtained in both the ECRHS I and II questionnaires 21. Body mass index (BMI, kg·m−2) was calculated as weight (in kg) divided by the square of height (in m) 21.

Information on smoking status was obtained at each ECRHS survey. Participants were divided into three categories: nonsmokers, ex-smokers and current smokers. To assess levels of ETS, participants were asked about regular exposure to cigarette smoke in the previous 12 months. Rhinitis was classified using the question: “Do you have any nasal allergies, including hay fever?” Occupational exposures were defined as exposure to biological dusts, mineral dusts, gases or fumes during the follow-up period 22 and classified as none, low or high exposure.

Statistical methods

Prevalence odds ratios (POR) were calculated for the prevalence estimates 23 and risk ratios (RR) for the cumulative incidence estimates. They were adjusted for age, sex and centre in the initial analyses; and for age, sex, country, BMI, family history of asthma, number of siblings, ETS, smoking status, rhinitis, respiratory infections before 5 yrs of age, mould or mildew in the home during the previous 12 months and high exposure to occupational pollutants in the fully

adjusted models, as with previous ECRHS analyses 13, 24. PORs were calculated using logistic regression and RRs using log–binomial regression. Tests for heterogeneity were assessed using meta-analysis while interaction terms were tested using likelihood ratio tests. Asthma score was analysed using a negative binomial regression model which models the ratio of score averages (i.e. incident risk ratio (IRR)) after adjusting for score at baseline.

Interaction terms were included to determine whether the associations of occupational class and educational level with health outcomes were the same in males and females. The interaction terms for educational level and occupational class were not significant (p = 0.21 and p = 0.18, respectively) for either asthma or bronchitis (p = 0.52 for educational level and p = 0.65 for occupational class). Thus, the results are presented with the data for males and females combined.

RESULTS

Prevalence

Table 1⇑ presents the characteristics of the study population. The overall prevalence of asthma was 10.4% (5.3% with atopy and 5.1% without atopy). The mean asthma score for the study population was 0.66. The prevalence of chronic bronchitis was 3.0%.

Almost one third of subjects belonged to occupational class I (managers and professionals) ranging from 15% in Verona (Italy) to 49% in Paris (France). Approximately 6.9% of subjects were unclassified. Of these, 44% were housepersons and 30% were currently employed but without an occupational ISCO code. The remainder were distributed amongst the unemployed, in poor health, retired or student categories.

Heterogeneity was assessed in the association between education level and asthma prevalence by measuring the prevalence of asthma against the percentage of low or medium educational level by country (adjusted for age, sex and centre). No heterogeneity was found for either the medium (p = 0.76 for heterogeneity) or low (p = 0.93 for heterogeneity) education categories.

Table 2⇓ presents the PORs for asthma (with and without atopy) and bronchitis in the minimally adjusted and fully adjusted models. There was a statistically significant increased risk of bronchitis in the low occupational group and with medium and low educational level, which were both also associated with an increased risk of asthma with no atopy. There was little change seen in the risk estimates in the fully adjusted model; however, the results were no longer statistically significant for bronchitis risk in the low occupational group.

Table 2—

Prevalence odds ratios(POR) of asthma (with or without atopy) and chronic bronchitis in European Community Respiratory Health Survey II participants by occupational class and education level

Treatment and healthcare utilisation among asthmatics (data not shown) were examined and no differences were found according to occupational class. With regard to educational level, some small nonsignificant differences were observed, e.g. asthmatics in the low education group were less likely to have been prescribed medicines for their breathing (OR 0.77; 95% confidence interval (CI) 0.51–1.2) or to have seen a doctor (OR 0.72; 95% CI 0.50–1.03) compared with those in the high education group.

Cumulative incidence

There were 298 new cases of asthma identified between ECRHS I and II, corresponding to a cumulative incidence of 5.3% over the 10-yr follow-up period. For the analyses of incident chronic bronchitis, 87 new cases were reported, corresponding to a cumulative incidence of 1.3% for the follow-up period.

As with the prevalence analyses, the present authors modelled effect estimates for heterogeneity to assess the association between asthma incidence and education group at the country level. For the medium educational and low educational levels there was no heterogeneity (p = 0.97 and p = 0.72, respectively) with asthma incidence. The present authors also assessed heterogeneity in the association between bronchitis and education group at the regional level (due to small numbers in some countries) composed of Scandinavia, Central Europe, Southern Europe and English-speaking countries. p-Values for heterogeneity were 0.18 and 0.52 for the medium and low education groups, respectively.

Generally, no large differences were observed for cumulative incidence of respiratory symptoms by occupational class (table 3⇓). Differences in cumulative incidence by educational level were more pronounced than for occupational class, with breathless while wheezing (p = 0.004), waking with chest tightness (p = 0.032) and attacks of shortness of breath after exercise (p<0.001) being more common in those individuals with a low educational level. The mean asthma score was highest in the low education group (p<0.001). The low education group had an increased incidence of bronchitis compared with the high education group (p = 0.008). Sensitisation to all of the allergens examined was highest in occupational class I, with the reverse pattern observed for educational level, where sensitisation was increased amongst those in the lower education groups.

Table 3—

Cumulative incidence of respiratory symptoms and sensitisation and asthma score by occupational class and education level between European Community Respiratory Health Survey I(1991–1992) and II (1999–2001)#

Table 4⇓ shows the cumulative incidence ratios for asthma (with and without atopy), chronic bronchitis and the average asthma score ratio. In the analyses adjusted only for sex, centre and age, there were no consistent patterns observed for asthma incidence by occupational class. Asthma without atopy was significantly associated with low educational level (RR 1.53; 95% CI 1.04–2.25). There was a statistically significant increased risk of incident bronchitis with both medium (RR 2.15; 95% CI 1.10–4.23) and low (RR 2.831; 95% CI 1.48–5.41) educational level.

The low occupational class group had a 43% higher mean asthma score (p<0.001) than the high occupational class group, and the low education group a 33% higher mean asthma score (p<0.001) than the high education group. Asthma score stratified by atopic status showed a similar pattern to that seen for asthma symptoms. When the asthma score for bronchitis was adjusted, it was found that bronchitis was highly correlated with the score (p<0.001) but this did not markedly change the asthma score risk estimates, which remained statistically significant. In the fully adjusted model, there was little change to the risk estimates for asthma score for both occupational class and educational level. Asthma (RR 1.40; 95% CI 1.03–1.89) and specifically, asthma with no atopy (RR 1.50; 95% CI 1.00–2.25) was significantly associated with low educational level. Bronchitis risk remained significant in both the medium and low education groups.

Table 4—

Cumulative incidence risk ratios(RR) of asthma (with or without atopy) bronchitis and asthma score for European Community Respiratory Health Survey II participants by occupational class and education level

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DISCUSSIONThe present authors examined the prevalence of respiratory symptoms in ECRHS II and the cumulative incidence of respiratory symptoms in relation to occupational class and educational level in the 10-yr follow-up period between ECRHS I and II. Prevalent bronchitis was increased in low occupational classes, while low educational level was associated with an increased risk of both prevalent and incident bronchitis. Lower socioeconomic groups tended to have a higher prevalence (particularly for asthma with no atopy) and incidence of asthma, with higher mean asthma scores. Known risk factors for asthma and chronic bronchitis explained only a small part of the observed differences by SES.

Some 3, 4, but not all 1, 25, studies have reported an increased risk of asthma with lower SES. ECRHS I found an increased prevalence of asthma in low SES groups 3, with the odds ratios being higher than those found in the current analyses. This difference is probably a combination of different sampling, since ECRHS II includes only a subset of ECRHS I, and improved living and working conditions and availability of treatments. It is unlikely that education directly affects the risk of developing respiratory symptoms, but it may capture long-term influences of early-life circumstances on adult health and is a predictor of future employment and income 26.

There are difficulties in the comparability of educational achievement across countries where changes in the education systems within populations and differences in the meanings of various educational categories between populations may vary 27. Previous ECRHS analyses of SES 3 used tertiles of educational level, based on the age of the subject at completion of full-time study, with the same cut-off points applied across the whole ECRHS study population. In the current analyses, tertiles specific for each country have been calculated to provide a relative measure of educational level and minimise problems associated with educational levels having different

meanings in different countries, which is only partially solved by adjusting for country. Using tertiles calculated over the whole ECRHS population yielded little difference in the risk estimates; however, the results were less consistent in terms of the direction of the gradient seen between high, medium and lower educational level and increased risk for all respiratory outcome measures compared with the results using country-specific tertiles.

Using IRR in the analyses, no association was found with occupational class and asthma risk, but an effect was seen when asthma symptoms were analysed as a continuous score. With a condition such as asthma, where there is a high prevalence and low incidence, bias due to disease misclassification may be substantial 7. The higher mean asthma scores with lower occupational class suggest that misclassification of asthma status at baseline may explain the absence of an association between asthma incidence and occupational class when the IRR measure was used.

The present findings are consistent with Montnémery et al. 1 who examined social position as a risk factor for asthma and chronic bronchitis in a random sample of 12,071 adults. Montnémery et al. 1 found an increased risk of bronchitis, but not asthma, in those individuals with a low social position compared with a middle/high social position. Chronic bronchitis has been found to be more consistently associated with lower social class 28 and unemployed people have a higher risk of bronchitis-type symptoms than their employed counterparts 20. Some of the observed associations with occupationally defined social class may be due to respiratory symptoms caused by occupational exposures 29, although several studies have reported that confounding by occupational exposure does not fully explain this association 30. A socioeconomic gradient has been reported with smoking, an important risk factor for bronchitis 30. No statistically significant interaction between either occupational class or educational level and smoking status was found, suggesting that the findings for SES and bronchitis were not dependent on smoking status.

The response rate for the current study was 59%, ranging 25–80%, across the participating centres and thus the potential for selection bias must be acknowledged. There were no differences between responding and nonresponding subjects by sex, but subjects from a high occupational class were more likely to respond (63%) than those from a low occupational class (57%). Responding subjects with asthma were slightly more likely to participate than those without asthma (62 versus 60%, respectively). The reverse pattern was seen for chronic bronchitis, with a higher proportion of those responding reporting no bronchitis at baseline (60%) compared with those with bronchitis (56%). In total, 22% of subjects were excluded due to missing data on atopy. The present authors assessed the effect of this by comparing the results among the study population, including those with missing atopy data, and among the population with atopy data. The results did not change, however, as no significant difference was found with occupational class (p = 0.88) or educational level (p = 0.81) for those with and without atopy data.

There may have been some misclassification of asthma or bronchitis, as defined by the questionnaire which has been previously validated against bronchial hyperresponsiveness 31. The overall effect of this type of misclassification would be to underestimate the true association of asthma or bronchitis with SES. Several potential explanatory factors were integrated in the fully adjusted models, including obesity, respiratory infections in childhood, exposure to allergens, smoking and exposure to ETS, which have been identified as being more common

among lower SES groups 8, 28. It is possible that some of these factors may be intermediate variables on the causal pathway between lower SES and asthma or bronchitis, and may be highly correlated with each other. In that case, it would be expected that risk associations would reduce with widening CI. However, there were no dramatic changes seen in either the risk estimates or CI between the minimally and fully adjusted models; e.g. the minimally adjusted RR estimate for asthma in the low education group was 1.32 (95% CI 0.99–1.77), which changed to 1.31 (95% CI 0.97–1.77) when BMI was added to the model. Inclusion of any one of the explanatory variables used in the fully adjusted model did not change the minimally adjusted risk estimate by >10%.

In conclusion, the present study identified lower educational level to be associated with an increased risk of prevalent and incident chronic bronchitis and also with an increased risk of prevalent and incident asthma with no atopy. Lower socioeconomic groups had higher mean asthma scores, suggesting that misclassification of asthma status at baseline and follow-up may explain some of the absence of an association between asthma incidence and occupational class in these analyses. Adjusting for potential explanatory variables related to socioeconomic status did not modify much of the association, suggesting that other factors in adult life or in childhood may mediate the occurrence of socioeconomic differences in respiratory disease.

Received August 3, 2006. Accepted December 17, 2006.

© ERS Journals Ltd

 

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Cast bronchitis in infants and childrenArticle Abstract:

Bronchitis, swelling in the bronchial tree of the breathing structures, can produce mucus. Cast bronchitis is characterized by the production of material that takes on the shape of breathing structures, much like a mold. These fibrous or mucus-like materials, called casts, differ from plugs of mucus by their shape and consistency. Although this type of bronchitis has been reported in adults, few cases have been found among children. It is suspected that many children with asthma-like bronchitis have bronchial casts. The clinical and X-ray findings of 72 children, three months to 5.5 years of age, with asthma-like or spastic bronchitis lasting more than two weeks and bronchial casts, are reported. Bronchial casts were found either in the stomach contents (from swallowing) or spontaneously coughed up. In 65 patients, the bronchitis lasted 10 to 24 months. An allergic response is not a likely cause, since laboratory indications of allergy were not found in the eight patients evaluated. Only one patient had a hypersensitive reaction, indicating an allergic condition. The casts were usually soft, hollow, white and had a branch-like appearance measuring 0.2 to 0.8 inches. They were composed of abnormal epithelial cells (the cells covering internal organs), inflammatory cells (which cause swelling) and some noncellular material. Viruses were not found in any of the 11 cast specimens studied. It is not known how the casts are formed. The strength of the casts depended on the ability of the epithelial cells to become attached. The more clumped the cells, the harder the cast. The epithelial cell transformation found in patients with cast formation is different from that caused by irritants

(smoke for example) and allergens. Cystic fibrosis, a genetic condition causing excess mucus production, was later confirmed in one patient. It is concluded that cast formation may be a common event in infants and children with obstructive bronchitis. (Consumer Summary produced by Reliance Medical Information, Inc.)

Gen Intern Med. 2002 March; 17(3): 230–234. doi: 10.1046/j.1525-1497.2002.10405.x.

PMCID: PMC1495016

Copyright 2002 by the Society of General Internal MedicineAntibiotic Treatment of Acute Bronchitis in SmokersA Systematic ReviewJeffrey A Linder, MD1 and Ida Sim, MD, PhD2

1Received from the General Medicine Division, Department of Medicine, Massachusetts General Hospital, Boston, Mass2The Division of General Internal Medicine, Department of Medicine, University of California–San Francisco, San Francisco, Calif.Address correspondence and requests for reprints to Dr. Linder: General Medicine Division, Massachusetts General Hospital, 50 Staniford St., 9th Floor, Boston, MA 02114 (e-mail: jlinder@partners.org).

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AbstractOBJECTIVECommunity physicians in the United States prescribe antibiotics to 80% to 90% of smokers with acute bronchitis. We performed a systematic review of the literature to determine the efficacy of antibiotics for smokers with acute bronchitis.DESIGNA MEDLINE search was done using the keywords bronchitis, cough, and antibiotics to identify English language articles published from January 1966 to September 2001. Randomized, placebo-controlled trials of antibiotics in previously healthy smokers and nonsmokers with acute bronchitis were included.MEASUREMENTS AND MAIN RESULTSFor each study, we abstracted information on design, size, inclusion criteria, patient characteristics, and outcomes. Of 2,029 articles in the original search, 109 relevant articles were retrieved and reviewed. There have been no studies specifically addressing antibiotic use in smokers with acute bronchitis. Nine randomized, placebo-controlled trials of antibiotics have included 774 patients and over 276 smokers. Lack of subgroup reporting for smokers precluded meta-analysis. In 7 trials, smoking status did not predict or alter patients' response to antibiotics. In one trial, trimethoprim/sulfamethoxazole resulted in less-frequent cough overall, but not among smokers. In another trial, erythromycin reduced symptom scores only among nonsmokers while antibiotic-treated smokers had a trend toward higher symptom scores.CONCLUSIONAlthough no trials have specifically addressed antibiotic use in smokers with acute bronchitis, existing data suggest that any benefit of antibiotics is the same or less for smokers than for nonsmokers.Keywords: bronchitis, antibiotics, smoking, systematic review

 Acute bronchitis is a self-limited upper respiratory condition in those without prior pulmonary disease, characterized by cough and lasting about 2 weeks.1 Sixty-five to eighty percent of patients with acute bronchitis receive antibiotics2–5 despite evidence antibiotics are at best marginally effective.1,6,7 This high rate of antibiotic use is increased even further by certain patient factors, such as smoking.Oeffinger et al. found that physicians report using antibiotics for 75% of nonsmoking patients with acute bronchitis but for 90% of smokers with acute bronchitis.8 Dosh et al. found that primary care practitioners, when treating patients with upper respiratory infections, sinusitis, and acute bronchitis, prescribed antibiotics to 64% of nonsmokers and to 81% of smokers.9

Despite this frequent practice, published reviews do not guide physicians faced with a smoker who has acute bronchitis.10–14 A recent joint position paper on antibiotic treatment of acute bronchitis by the Centers for Disease Control and Prevention and the American College of Physicians–American Society of Internal Medicine makes no mention of smoking status affecting the decision to prescribe antibiotics.15,16 We performed a systematic review of the literature to determine if antibiotics are effective in smokers with acute bronchitis.

METHODSInclusion CriteriaStudies were included if they were placebo-controlled, randomized trials of antibiotics in adult patients with acute bronchitis. We defined acute bronchitis as a productive cough of less than a month's duration in a patient without history of cardiac or pulmonary disease and no clinical signs of pneumonia. Patients could have rhonchi or wheezes on auscultation. Chest radiographs to rule out pneumonia were not required. Trials including patients with acute exacerbation of chronic bronchitis were excluded.Search StrategyA medline and pre-medline search was done using the keywords bronchitis or cough and antibiotics to identify trials, reviews, letters, and editorials published in English between January 1966 and September 2001. Titles and abstracts were screened for suitability, and those deemed appropriate were retrieved and reviewed. References of retrieved articles were examined to identify additional studies.Data Abstraction and AnalysisWe abstracted information on study design, patient characteristics, enrollment criteria, main results, and results in smokers. We evaluated strength of study design and follow-up using the method of Jadad et al.17

For continuous outcomes, when available, we calculated point estimates and 95% confidence intervals using the 2-sample t test. To compare adverse effects of antibiotics with placebo we used Fisher's exact test.

RESULTSSearch ResultsThe search yielded 2,029 articles. On the basis of title and abstract, 1,920 articles did not meet inclusion criteria We obtained the remaining 109 articles focusing on acute bronchitis. Among these, there were 9 randomized, placebo-controlled studies of antibiotics in smokers and nonsmokers. No studies specifically addressed antibiotic use in smokers.Because the data on smoking were not reported uniformly or in sufficient detail, we were not able to perform a quantitative meta-analysis. Instead, we present a qualitative review of the 9 placebo-controlled trials of antibiotic use for acute bronchitis, focusing on the results in smokers where available.Study CharacteristicsThe 9 placebo-controlled trials involved a total of 774 patients and over 276 smokers (Table 1).18–26 The proportion of smokers in these trials ranged from 32% to 75%, averaging 49% overall. The mean age of patients in these trials ranged from 30 to 43 years old. One trial did not report the percentage of smoking patients or age distributions.18 The mean quality score by the method of Jadad and colleagues was 3.9 (range 3 to 5) out of a maximum of 5, indicating some deficiencies in blinding, randomization, or follow-up.

Table 1Randomized Placebo-controlled Trials of Antibiotics in Smokers with Acute Bronchitis

The trials evaluated 3 different antibiotics: doxycycline, trimethoprim/sulfamethoxazole (TMP/SMX), and erythromycin. Six trials assessed some combination of 3 main continuous outcomes: duration of cough, duration of yellow sputum, and time off work. The remaining 3 trials assessed other outcomes: activity level, symptom scores, physician assessment, and duration of fever.Efficacy of AntibioticsIn 5 of the 9 studies, antibiotics showed no overall benefit. In the trials by Stott and West,18

Williamson,20 Hueston,24 and Brickfield et al.21 smoking status did not alter the lack of response to antibiotics. The trial by Brickfield et al. demonstrated a trend toward decreased symptom scores only among nonsmokers receiving erythromycin. Among smokers, those receiving erythromycin had significantly worse scores for headache on day 1 and chest congestion on days 1, 2, and 3 compared to smokers receiving placebo. Smokers receiving erythromycin did not have significantly better scores than smokers receiving placebo for any outcome, including mean number of days to symptom improvement or physician assessment. The study by Scherl et al. did not stratify by smoking status.23

One of the 9 trials, by Franks and Gleiner, which evaluated TMP/SMX, showed a reduction in the presence of cough over 7 days in all patients treated (93% in the TMP/SMX group versus 99% in the placebo group; 1-tailed P = .05).19 Most other outcomes, including cough frequency, cough amount, and activity level, trended toward benefit among all patients taking TMP/SMX. Among smokers, the authors found no statistical benefit of TMP/SMX for any outcome.Three of the 9 randomized, placebo-controlled trials report decreased duration of daytime cough, days off work, and sputum production score for antibiotic-treated patients.22,25,26 These benefits represented less than 1 day of coughing, less than 1 day off work, and a decrease in sputum production scores of unclear clinical significance. For all 3 trials, smoking status neither enhanced nor diminished patients' response to antibiotics.Adverse effects averaged 11% (range among trials 0% to 37%) in the placebo-treated patients and 16% (range among trials 6% to 36%) in the antibiotic-treated patients in 7 trials (P = .08). The most frequent adverse effects were gastrointestinal upset, nausea, and vomiting. Two trials did not report adverse effects.23,24 No trial stratified adverse effects by smoking status.

DISCUSSIONAntibiotic prescription for smokers with acute bronchitis is common, but our review of 9 placebo-controlled trials suggests—contrary to conventional wisdom—that smokers derive no greater benefit from antibiotics than do nonsmokers. The results of 2 trials suggested that smokers may benefit less from antibiotics than do nonsmokers.Brickfield and colleagues demonstrated consistent trends toward decreased symptom scores among only nonsmokers receiving erythromycin.21 They also found increasing

symptom scores for smokers receiving erythromycin compared to smokers receiving placebo. Because all differences occurred on or before day 3, baseline differences between groups may explain this finding. Franks and Gleiner19 found a decreased proportion of patients with cough among those taking TMP/SMX, but there was no benefit when patients were stratified by smoking status.These results are limited by the small sample sizes of the trials reviewed. Individually, these trials may have lacked statistical power to detect differences between subgroups. The largest of the trials included only 212 patients with an unknown number of smokers.18 Meta-analysis of the 276 smokers included in the other trials was not possible due to insufficient reporting stratified by smoking status.Another limitation of this study is that these results apply only to relatively healthy patients. Patients who participated in these trials were fairly young and had no comorbid cardiac or pulmonary disease. In contrast, antibiotics have been shown to be beneficial for patients with acute exacerbations of chronic bronchitis, regardless of smoking status.27

Controversy over antibiotics has overshadowed other interventions with potential benefits for patients with acute bronchitis, such as β-agonists. At 1 week, 41% of patients randomized to oral albuterol and 82% of patients randomized to erythromycin were still coughing (P = .004).28 Of 17 smokers in this trial, 45% given albuterol and 100% given erythromycin were still coughing at 1 week (P = .03). In a randomized, placebo-controlled trial, 78% of patients receiving inhaled albuterol returned to work at day 4, compared to 52% in the placebo group (P = .05).24 At 1 week, 61% of patients given inhaled albuterol were still coughing, compared to 91% of patients in the placebo group (P = .02). In another study, inhaled fenoterol reduced symptoms for patients with wheezing on auscultation, bronchial hyper-responsiveness, or evidence of airflow obstruction.29 Of 36 smokers in this trial, 72% in the fenoterol group and 48% in the placebo group had a reduction in total symptoms on day 7 (P = .19). Although β-agonists are generally well-tolerated, patients should be warned of common adverse effects, such as tremulousness, nervousness, or palpitations.30

Physicians should use an episode of acute bronchitis to counsel patients to stop smoking. Smokers should be told they are at risk for a prolonged course of illness31 and of the risk of progression to chronic bronchitis if they continue smoking.32 Physicians should offer a referral for counseling and offer nicotine replacement if patients are serious about quitting.Given the current evidence, it is unlikely that antibiotics are more useful in smokers with acute bronchitis than nonsmokers. To definitively determine this, further trials are warranted in smokers with acute bronchitis. These trials should have well-defined inclusion criteria, have sufficient power to detect meaningful clinical differences between groups, and use validated outcome measures. In the meantime, smokers and nonsmokers alike should use symptomatic treatment, including inhaled β-agonists, cough suppressants, analgesics, and antipyretics,15,16 and should avoid the use of antibiotics for acute bronchitis.AcknowledgmentsThe authors would like to thank Daniel E. Singer, MD and Mary McNaughton Collins MD, MPH for critical review of an earlier version of the manuscript. Special thanks to Stephen Bent, MD for his assistance in the conception of this work and assistance with the literature review.Dr. Linder was supported by National Research Service Award 5T32PE11001-12.REFERENCES

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