Central Journal of Family Medicine & Community Health

Cite this article: Pavlov N, Duvnjak JP (2015) Asthma – Examples from Practice. J Family Med Community Health 2(4): 1040.

Abstract

Asthma is the most common chronic disease of childhood with increasing prevalence particularly in children. Many guidelines, especially Global Initiative for Asthma (GINA) and Practical Allergology (PRACTAL) have had a great impact on improvement in diagnostic and treatment of asthma in children. In children, as in adults assessment of asthma symptom control is based on symptoms, activities limitation and use of rescue medication. We presente six children with different problems in asthma treatment in attempt to help primary care physician to identify possible options for care improvement of this population.

*Corresponding authorNeven Pavlov, Department of Pediatrics, University Hospital Centre Split, Spinciceva 1, 21000 Split, Croatia, Email:

Submitted: 06 April 2015

Accepted: 27 May 2015

Published: 29 May 2015

Copyright© 2015 Pavlov et al.

OPEN ACCESS

Keywords•Child•Asthma•Family physician•Practical problem

Case Report

Asthma – Examples from PracticeNeven Pavlov* and Jasna Petric Duvnjak Department of Pediatrics, University Hospital Centre, Croatia

ABBREVIATIONS ACQ: Asthma Contol Questionnaire; BH: Bronchial

Hyperreactivity; BT: Bronchodilator Test; BTM: Methacholine Bronchoprovocation Test; c-ACT: Childhood Asthma Control Test; DP: Dermatophagoides Pteronyssinus; ECP: Eosinophil Cationic Protein; FeNO: Fraction of NO in exhaled air; GINA: Global Initiative for Asthma; ICS: Inhaled Corticosteroid; INCS: Intranasal Corticosteroid Spray; LTRI: Inhibitor Leucotriene Receptors; PRACTAL: Practical Allergology; SABA: Short-Acting Beta2-Agonist; USA: United States of America; FP: Family Phisician; PCP: Primary Care Physician; CHIF: Croatian Health Insurance Fund; UNICEF: United Nations International Children’s Emergency Fund; PHC: Primary Health Care.

INTRODUCTIONAsthma is the most common chronic disease of childhood.

Generally, the prevalence of asthma is increasing, particularly in children [1]. In Croatia asthma prevalence is high. It affects 5% of general population (220.000 people) and aproximatly 80-100.000 children. In Primorje - Gorski Kotar County in west Croatia high increase in asthma prevalence have been detected, from 8.4% in 2001 – 2002 to 14.2% in 2009-2010 [2]. High asthma prevalence is related with urban life style (air pollution, smoking, overweight etc.). Many guidelines, especially Global Initiative for Asthma (GINA) and Practical Allergology (PRACTAL) have had a great impact on improvement in diagnostic and treatment of asthma in children. Finally good asthma control results in avoidance of chronic lung damage and better long term outcomes [3,4]. Why then despite wide accessibility of guidelinces, different medication strategies and highly developed primary and secondary health care system we still have prominent number of children with inadequate threated and uncontrolled asthma who aren’t supervised by pulmonology and allergology specialist? I hope that examples from my practice will resolve some of this questions.

What is reccomended by guidelines?

GINA in Chapter of Assessment of asthma advices to asses:

1. symptom control

2. Future risk of adverse outcomes together with asses of treatment issues: correct inhaler technique, adherence (previously complience), side effects and commorbidities [4].

Assessment off the patient’s asthma control level is made individually.

Patient with one risk factor, for exemple good symptom control but risk for future exacerbations because of severe exacerbation in last year, request different treatment aproach [4].

In children, as in adults assessment of asthma symptom control is based on symptoms, activities limitation and use of rescue medication. Many children with poor controled asthma avoide exercise so their asthma seems to be good controlled. This lack of physical activities in young age can lead to obesity. In process of asthma assessment it is necessery to include parents because of different problem perception. Parents may report irritability, tiredness and mood changes in uncontrolled asthma [4].

There are several asthma control scores for the children:

- Childhood Asthma Control Test (c-ACT), with questions for parents and children [5]

- Asthma Contol Questionnaire (ACQ) [6].

These test results may correlate in some extend with each other and with GINA classification of symptoms control (Table 1) [4].

CROATIAN CHILDREN HEALTH CARE According to Croatian Ministry of Health legislation

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pediatrician are responsible for health care of infants, children, and adolescents (the age limit ranges from birth up to 18 years of age). In parts of country were pediatricians are not available, general practitioners or family care physicians (Primary Care Physicians – PCP) provide healthcare for the children. Contracting model between pediatricians in primary care system and Croatian Health Insurance Fund (CHIF) allowe pediatricians to provide healthcare for 1190 children under age of 7, and expectionally for school children (age 7 to 18) if there is not enough children under age of 7 [7]. In practise CHIF make contract for health insurance for 300 children between age 7 and 18 and that is a total of 1500 children. There is almost always children who can’t be in care of pediatricians because contracted limits are exceed and they are in care of PCP, due to UNICEF’s (United Nations International

Children’s Emergency Fund) Croatia data in whole country approximatly 500 000 school children and adolescents [8].

There is a question of competency and healthcare quality provided to children by PCP. Pediatrician specialization duration in Croatia is 5 years, and PCP education in pediatrition is about 3 moths [9,10]. There is a strong recomendation of Croatian Pediatric Society that children under age of 18 must be under pediatrician’s care because they are most educated and competent in providing children healthcare. Recent political tendency in Croatia is to dismiss pediatricians form Primary Health Care (PHC). Croatian Society for Paediatric Pulmonology was discussing about this problem on XXVIII Meeting in Sinj (8th to 10th May, 2015) and decide to conduct survey about education and competency of PHC Physicians (Pediatricians and PCP) that

Table 1: GINA assessment of asthma control in adults.

A. Asthma symptom control Level of asthma symptom control

Well Partly Uncontrolled

In the past 4 weeks, has the patient had:

Daytime asthma symptoms

more than twice/week? Yes/No

Any night waking due to asthma? Yes/No

Reliever needed for symptoms* more None 1-2 3-4

than twice/week? Yes/No of these of these

Any activity limitation due to asthma? Yes/NoB. Risk factors for poor asthma outcomes

Asses risk factors at diagnosis and periodically, particularly for patients experiencing exacerbations. Measure FEV1 at start of treatment, after 3-6 months of controller treatment to record the patient’s personal best lung function, then periodically for ongoing risk assessment.

Potential modifiable independent factors for flare-ups (exacerbations)

• Uncontrolled asthma symptoms [8]

• Excessive SABA use (>1 x 200-dose canister/month) [9]

• Inadequate ICS: not prescribed ICS; poor adherence [10]; incorrect technique [11]

• Low FEV1, especially if <60 % predicted [12,13]

• Major psychological or socioeconomic problems [14]

• Exposure: smoking [13], allergen exposure if sensitized [13]

• Comorbidities: obesity [15], rhinosinusitis [16], confirmed food allergy [17]

• Sputum or blood eosinophilia [18,19]

• Pregnancy [20]

Other major independent risk factors for flare-ups (exacerbations)

• Ever intubated or in intensive care unit for asthma [21]

• ≥1 severe exacerbation in last 12 months [22]

Having one or more of these risk factors increases the risk of exacerbations even is symptoms are

Well controlled.Risk factors for medication side – effects

• Systemic: frequent OCS; long - term, high dose and/or potent ICS; also taking P450 inhibitors [27]

• Local: high - dose or potent ICS [27,28]; poor inhaler technique [29]Abbreviations: FEV1: forced expiratory volume in 1second; ICS: inhaled corticosteroid; OCS: oral corticosteroid; P450 inhibitors: cytochrome

P450 inhibitors such as ritonavir, itraconazole, ketoconazole; SABA: short-acting beta2- agonist.

* Excludes reliever taken before exercise.

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will be the base in their efforts to Croatian Ministry of Health for improving quality of their education.

PRACTICAL PROBLEMSCroatian Society for Preventive and Social Pediatric Report

from April 2014 emphasis need for increased responsability of primary care medical personel forward to health quality improvement. Primary care physician is obligated to continuous medical education and certificates of medical education are requested every 6 years for relicensing to Croatian Medical Chamber. At same time physician is fully independent in his work and without medical supervising. Unfortunatly, in our practise, we are still witnessing underdiagnosed, undertreated and uncontrolled child with asthma. Explanation given to parents usually are: “there is no need for further diagnosis because child will be treated with same medication anyway and eventually overgrowth sickness“. Usually they seek help from Allergology and Pulmology specialist in the age of 14, or before when they change primary care doctor from Pediatrician to Family Care physician. Often we see patients, never properly diagnosed, from our city treated asthma with antibiotics, parenteral corticosteroid and SABA inhalation. It is question of medical responsability of their Pediatrician. How can we stimulate them to accept current guidelines in diagnosis and treatment of child with asthma. Patient - doctor relationship is very fragile and based on trust. It starts with child and parents (or other family members) education about asthma. Satisfied interaction between physician and patient will result in preventive and therapeutic measures success. Patient decision to cease medical treatment or to „step down“ asthma medication is usually result of comunication problem with physician. That situation is unfortunatly good base for alternative, nonconventional treatmens.

Patient 1

M. S., twelve-year-old girl was diagnosed asthma and atopic rhinitis from young age. Symptoms were cough, dyspnea during exercise and weather changes… Skin prick test was positive on house dust mite (Dermatophagoides Pteronyssinus, D.P.), ragweed (Ambrosia), feather, European black pine (Pinus nigra). Eosinophil blood count was high (10 %) with absolute number 880/mm3 (normally <280 eosinophils). On spirometer, we found mild obstructive airflow disturbances with striking bronchodilator test (BT) of bronchial reversibility with salbutamol (Figure 1). Other diagnostic tests were recommended (IgE, specific serum IgE to grass pollen, house dust mite and eosinophil cationic protein (ECP). During medical examination, obstructions of the nose with wheezing during lung auscultation have been found. ACT score was 19 (uncontrolled asthma). After explanation of preventive measures and allergy avoidance combination of low dose fluticason propionat and salmeterol (100 µg/ 50 µg discus, 2 x 1 breath / day), intranasal corticosteroid spray (INCS) and short-acting beta2-agonist as needed (SABA). After symptoms disapearing, after 3 months of therapy, patient ceased medication and seek advice from local herbalist. Often patients seek alternative treatment (herbal tee, special diet, green honey etc.) that is problem because they stop to take their medicine. About 10 days later she expirienced breathing problems with cough. She had difficulties with nose obstruction and marked breathing obstruction aproved by spirometry. Fraction of NO in exhaled air

(FeNO) was 58.30 ppb (normal value < 22), as a marker of bad allergic inflamation control. Parents realised effects of their bad decision and agreed to start again with medical treatment.

Patient 2

T. Lj. 7 - years old boy, previously controlled in our Allergologic Practise because of atopic dermatitis, atopic rhinitis and asthma. He was allergic to house dust mite and weed pollen (IgE: 1606 kU/L, specific IgE: D.P. (d1): class 3 (12.9 kU/L), secale cereale (g12): class 2 (2.47 kU/L), ECP: 48.8 µg/L (normaly < 15.6). Spirometry: moderate mixed ventilation disturbance with positive post bronchodilation test. Treatment with low dose inchaled corticosteroid (ICS, fluticason propionat a 50 µg 2 x 1 breaths trow spacer) stopped symptoms. Parents reported exacerbation after every interruption of ICS adviced by Pediatrician because of „corticosteroid noxiousness“. Further treatment was discus fluticason propionat a 100 µg: 1 breath in the evening. A significant proportion of parents whose children were on inhaled prophylaxis had concerns towards the use of inhaled therapy, especially ICS [33]. Eduaction of these parents are esential for asthma control improvement.

Patient 3

I. P., 16 – years old boy, from early childhood treated because of asthma, atopic rhinitis and pectus infundibuliforme. He was allergic to weed pollen and house dust mites verified with skin prick test, IgE and specific IgE. Repeated spirometry revealed moderate obstruction with positive post bronchodilator test, FeNO was 53.11 ppb (Figure 2). Attempting to find a cause why doubleing a dose of combination medicine (fluticason propionat 100 µg/salmeterol 50 µg to fluticason propionat 200 µg/salmeterol 50 µg,) doesn’t stopped asthma exacerbation we were astounded because our patient start smoking! Metacholine bronchoprovocation test (BTM) showed noticeable bronchial hyperreactivity (BH): PD20FEV1 < 0.0042 µg cummulative (normaly >1400 µg) [34]. Mother confessed ignoring measures of allergen avoidance (carpets and curtains are still in boys bedroom). Without planned patients and parents education about allergen and irritance avoidance, active and pasive smoking and indispensable longterm antiinflamantory treatment necesser for bronchial hyperreactivity normalisation it will be impossible to achieve goals of asthma control.

Patient 4

D. G., 11 – yeras old girl with positive family history for atopy (uncle, grandfather and great grandfather were asthmatic) and diagnosed asthma and atopic rhinitis was allergic to house dust mite and olive tree pollen. IgE: 1566 kU/L, specific IgE D. P. (>100 kU/L), ECP >200 µg/l, Dünger 1000; 840; 710 eo/mm3, nose smear: 4 - 6 eosinophils. Spirometry was normal except positive BT of small airways. Patient was previously treated with inhibitor leucotrien receptors (LTRI) montelucast 5 mg during 6 months and after that by mistake with lower dose (4 mg). After 3 months on regular check in dose was corrected. BTM showed marked bronchial hyperreactivity (PD20FEV1 < 0.0022 µg) (Figure 3). Nobody involved in medical treatment made comments about change in montelucast dose. Family physician and pharmacist trusted authority of allergologist and mother doesn’t call to check dose. Our opinion is that pharmacit must be in line with asthma

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Figure 1 Flow – volume curve and bronchodilator test in 12-year-old girl with asthma.

control guidelines because they sometimes confuse patients and there parents (discurage comments about treatment, fear of corticosteroid side effects).

Patient 5

M. Š., 8 – years old boy with positive family history for atopy (brother have allergic rhinitis) was checked with allergologist in May 2013, because of persistent cough duration more than a month and episodes of dyspnea revelied with salbutamol inhalation. On clinical exam partial nose obstruction and wheezing with prolonged exhalation were found. Skin prick test was positive on house dust mite, grass pollen and feather, IgE:

1046 kU/L, specific IgE D. P. (d1): 6 (>100 kU/L), phleum pratense (g6): 4 (31.1 kU/L), ECP: >200 µg/L (normaly <16.6). Dünger test: 2000 eo/mm3, eosinophilia in peripheal blood (22 %) and many eosinophills in nose smear. Spirometry was normal, BT negative. Boy was recommended to avoide allergens and start treatment with intranasal corticosteroid spray (mometason) during 1 month and fluticason propionat 100 µg discus 2 x 1 breaths, normal saline nasal drops and antihistaminic as needed. Boy was taken medicine unregullary until few days before follow up exam. Clinical exam was normal but labarotory findings weren’t: Dünger: 1200 eo/mm3, eosinophilia in peripheral blood 13%, FeNO 28.09 ppb. That example emphasis need to be suspicious

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Figure 2 Increased FeNO values in boy with asthma.

about patients complience or self „step down“ medication in case of slow normalisation of laboratory findings or symptoms.

Patient 6

A. G., 14 – year old girl was transported with emergency helicopter medical flight from nearby island in status asthmaticus. Father and grandmother had asthma. At age of 5 girl was diagnosed allergy on animal hair, house dust mite and grass pollen. They don’t posses any medical documentation. Despite treatment of „mild asthma“ with LTRI (montelucast), ICS (fluticason) and combination (fluticason and salmeterol) surprisingly she never did spirometry. She wasn’t taken any medication last 5-6 years. In October 2013 she had breathing problems treated with antibiotics

and SABA. After that she was without symptoms and physical active. Family physician sugested cesation of breathing problems in puberty, but everytime she had cold she needed symptom reliever (SABA). Present illness started 4 days before admittion to hospital with virosis symtoms (abdominal cramps, vomiting, sore throat, cough). Emergency medicine physician on island started treatment with SABA inhalation, parenteral corticosteroid and antibiotics. Chest radiography showed hyperinflation of left lung with low right lung base transparency and shift of hearth on the right side because of atelectasis. Emergency treatment with supplemental oxygen and restoration of fluid was started and a girl was transported to hospital. Diagnostic and therapeutical aims of good control asthma together with asthma control plan

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Figure 3 Bronchoprovocation test with metacholine with in marked bronchial hyper-reactivity in girl with asthma.

were discussed afterwords with girl and parents. This was example were additional education of PCP can change quality of their healthcare.

CONCLUSONAsthma is example of disease dependent on timely diagnostic

procedures, efficient preventive measures, correct long term antinflammatory medications with good self controll and support of parents, family physician and community. Education is key stone of asthma treatment. Parents and patient with clear message about goals of asthma treatment are essential part and most important associate in physician patient interaction. Primary Care Physician (Pediatrician and Family Physician) responsibility as connection between child with asthma and pediatrician allergologist – pulmonologist subspecialist is underestimated. PCP have very important role in patient education and best possible treatment according current guidelines of child with asthma. Only together we can improve asthma outcomes in children.

REFERENCES1. Loddenkemper R, Gibson GJ, Sibille Y. Asthma in childhood. European

lung white book. The first comprehensive survey on respiratory health in Europe. Scheffield: European Respiratory society Journals. 2003; 26-33.

2. Banac S, Rožmanić V, Manestar K, Korotaj-Rožmanić Z, Lah-Tomulić K, et al. Rising trends in the prevalence of asthma and allergic diseases among school children in the north-west coastal part of Croatia. J Asthma. 2013; 50: 810-814.

3. Bacharier LB, Boner A, Carlsen KH, Eigenmann PA, Frischer T, Götz M, Helms PJ. Diagnosis and treatment of asthma in childhood: a PRACTALL consensus report. Allergy. 2008; 63: 5-34.

4. Polosa R, Bellinvia S, Caruso M, Emma R, Alamo A, Kowalski ML, et al. Weekly low-dose methotrexate for reduction of Global Initiative for Asthma Step 5 treatment in severe refractory asthma: study protocol for a randomized controlled trial. Trials. 2014; 15: 492.

5. Juniper EF, Gruffydd-Jones K, Ward S, Svensson K. Asthma Control Questionnaire in children: validation, measurement properties, interpretation. Eur Respir J. 2010; 36: 1410-1416.

6. Chipps B, Zeiger RS, Murphy K, Mellon M, Schatz M, Kosinski M, et al. Longitudinal validation of the Test for Respiratory and Asthma Control in Kids in pediatric practices. Pediatrics. 2011; 127: 737-747.

7. The decision on the bases for concluding agreements on the

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Pavlov N, Duvnjak JP (2015) Asthma – Examples from Practice. J Family Med Community Health 2(4): 1040.

Cite this article

implementation of health care from the compulsory health insurance. Official Gazette 156/13 ; ARTC . 12 , subsec . 21st and 22nd.

8. Brajša-Žganec A, Franc R, Merkaš M, et al. Analiza stanja prava djece i žena u Hrvatskoj. Zagreb: Ured UNICEF-a za Hrvatsku; 2011; 41.

9. Program specijalizacije iz pedijatrije.

10. Program specijalizacije iz obiteljske medicine.

11. Haselkorn T, Fish JE, Zeiger RS, i sur. Consistently very poorly controlled asthma, as defined by the impairment domain of the Expert Panel Report 3 guidelines, increases risk for future severe asthma exacerbations in The Epidemiology and Natural History of Asthma: Outcomes and Treatment Regimens (TENOR) study. J Allergy Clin Immunol. 2009; 124: 895-902.e1-4.

12. Suissa S, Ernst P, Boivin JF, Horwitz RI, Habbick B, Cockroft D, et al. A cohort analysis of excess mortality in asthma and the use of inhaled beta-agonists. Am J Respir Crit Care Med. 1994; 149: 604-610.

13. Ernst P, Spitzer WO, Suissa S, Cockcroft D, Habbick B, Horwitz RI, et al. Risk of fatal and near-fatal asthma in relation to inhaled corticosteroid use. JAMA. 1992; 268: 3462-3464.

14. Melani AS, Bonavia M, Cilenti V, Cinti C, Lodi M, Martucci P, Serra M. Inhaler mishandling remains common in real life and is associated with reduced disease control. Respir Med. 2011; 105: 930-938.

15. Fuhlbrigge AL, Kitch BT, Paltiel AD, Kuntz KM, Neumann PJ, Dockery DW, et al. FEV(1) is associated with risk of asthma attacks in a pediatric population. J Allergy Clin Immunol. 2001; 107: 61-67.

16. Osborne ML, Pedula KL, O’Hollaren M, Ettinger KM, Stibolt T, Buist AS, et al. Assessing future need for acute care in adult asthmatics: the Profile of Asthma Risk Study: a prospective health maintenance organization-based study. Chest. 2007; 132: 1151-1161.

17. Sturdy PM, Victor CR, Anderson HR, Bland JM, Butland BK, Harrison BD, et al. Psychological, social and health behaviour risk factors for deaths certified as asthma: a national case-control study. Thorax. 2002; 57: 1034-1039.

18. Fitzpatrick S, Joks R, Silverberg JI. Obesity is associated with increased asthma severity and exacerbations, and increased serum immunoglobulin E in inner-city adults. Clin Exp Allergy. 2012; 42: 747-759.

19. Bousquet J, Khaltaev N, Cruz AA, Denburg J, Fokkens WJ, Togias A, et al. Allergic Rhinitis and its Impact on Asthma (ARIA) 2008 update (in collaboration with the World Health Organization, GA(2)LEN and AllerGen). Allergy. 2008; 63: 8-160.

20. Burks AW, Tang M, Sicherer S, Muraro A, Eigenmann PA, Ebisawa M,

et al. ICON: food allergy. J Allergy Clin Immunol. 2012; 129: 906-920.

21. Belda J, Giner J, Casan P, Sanchis J. Mild exacerbations and eosinophilic inflammation in patients with stable, well-controlled asthma after 1 year of follow-up. Chest. 2001; 119: 1011-1017.

22. Ulrik CS. Peripheral eosinophil counts as a marker of disease activity in intrinsic and extrinsic asthma. Clin Exp Allergy. 1995; 25: 820-827.

23. Murphy VE, Clifton VL, Gibson PG. Asthma exacerbations during pregnancy: incidence and association with adverse pregnancy outcomes. Thorax. 2006; 61: 169-176.

24. Turner MO, Noertjojo K, Vedal S, Bai T, Crump S, Fitzgerald JM. Risk factors for near-fatal asthma. A case-control study in hospitalized patients with asthma. Am J Respir Crit Care Med. 1998; 157: 1804-1809.

25. Miller MK, Lee JH, Miller DP, Wenzel SE; TENOR Study Group. Recent asthma exacerbations: a key predictor of future exacerbations. Respir Med. 2007; 101: 481-489.

26. O’Byrne PM, Pedersen S, Lamm CJ, Tan WC, Busse WW; START Investigators Group. Severe exacerbations and decline in lung function in asthma. Am J Respir Crit Care Med. 2009; 179: 19-24.

27. Lange P, Parner J, Vestbo J, Schnohr P, Jensen G. A 15-year follow-up study of ventilatory function in adults with asthma. N Engl J Med. 1998; 339: 1194-1200.

28. Baur X, Sisgaard T, Aasen TB, i sur. Guidelines for the management of work –related asthma? Erratum appears in Eur Respir J. Eur Respir J. 2012; 39: 529-45.

29. Ulrik CS. Outcome of asthma: longitudinal changes in lung function. Eur Respir J. 1999; 13: 904-918.

30. Raissy HH, Kelly HW, Harkins M, Szefler SJ. Inhaled corticosteroids in lung diseases. Am J Respir Crit Care Med. 2013; 187: 798-803.

31. Foster JM, Aucott L, van der Werf RH, van der Meijden MJ, Schraa G, Postma DS, et al. Higher patient perceived side effects related to higher daily doses of inhaled corticosteroids in the community: a cross-sectional analysis. Respir Med. 2006; 100: 1318-1336.

32. Roland NJ, Bhalla RK, Earis J. The local side effects of inhaled corticosteroids: current understanding and review of the literature. Chest. 2004; 126: 213-219.

33. Chan PW, DeBruyne JA. Parental concern towards the use of inhaled therapy in children with chronic asthma. Pediatr Int. 2000; 42: 547-551.

34. Pavlov N. Lung function testing and monitoring children with asthma. Paediatr Croat. 2007; 51: 85-90.