Phytotherapy Review & Commentaryby Kerry Bone, FNIMH, FNHAA

P.O. Box 713 • Warwick QLD 4370, Australia+61 7 4661 0700 • Fax +61 7 46610788 • www. mediherb.com

FNIMH - Fellow, National Institute of Medical Herbalists (UK)FNHAA = Fellow, National Herbalists Association of Australia

Phytotherapy for Lower RespiratoryDisease: Basic Principles

Traditional herbalstrategies for treatinglung disease are foundedon supporting and

tonifying the innate protective resources. This is one area wherethe divide between traditional and modern approaches isparticularly great. There are very few modern endorsements ofearly treatment strategies. Modern medical science, which atfirst embraced such agents in the earlier part of this century,now sees no role for their use. For example, modern editions ofMartindale's Extra Pharmacopoeia claim that: "There is littleevidence to show that expectorants are effective." Some moderndrugs may have expectorant activity, such as bromhexine, butthey are usually referred to as 'mucolytic'. The impact oftraditional remedies on the respiratory system is relatively poorlyresearched. Reliable external measures of change in mucosalfunctions are elusive; many respiratory diseases are either self-limiting or are among some of the most persistent conditions inthe clinic'

However, while the traditional herbal approach is somewhatlacking in scientific support, it is not without a rational basis.This article will examine some important herbal conceptsinvolved in supporting the innate defenses of the lungs duringinfection. The key concept of expectorants will be discussed indetail, with a focus on the classification of expectorants and tbescientific investigations into their effects.

ExpectorantsPart of the problem with expectorants probably arises from

confusion over their definition. Another aspect of the dismissalof expectorants stems from the difficulties involved withmeasuring their efficacy.

The four definitions of expectorants given below highlightthe difficulties. The dictionary meaning is only concerned withthe actual oral production of phlegm or sputum. Since themajority of mucus produced from the lungs is swallowed, thisdefinition is clearly unsatisfactory. Definitions from thepharmacologists Boyd and Lewis are more useful but probablythe best definition comes from Brunton, a 19th centurypharmacologist.

Oxford Dictionary "Promoting the ejection of phlegm bycoughing or spitting,"

Boyd (1954) "An expectorant may be pharmacologically definedas a substance which increases the output of demulcentrespiratory tract fluid,"

Lewis (1960) "Expectorants increase the secretions of therespiratory tract and so reduce the viscosity of the mucuswhich can then act as a demulcent. By virtue of the presenceof increased quantities of fluid mucus, expectorants producea "productive cough" which is less exhausting and less painfulto the patient."

Brunton (1885) "Remedies which facilitate the removal ofsecretions from the air passages. The secretion may berendered more easy of removal by an alteration in itscharacter or by increased activity of the expulsivemechanism."

Why Expectorants?Many respiratory conditions are characterized by abnormal

mucus (catarrh) which can narrow airways. This abnormal mucusmay be thick and tenacious and hence very difficult to clear fromthe airways. If expectorants can render this catarrh more fluidand/or assist in its expulsion, then a clinical benefit should beachieved.

Expectorants can help to relieve debilitating cough. Thepresence of an irritation in the airways (sucb as tenaciousabnormal mucus) invokes the cough reflex, (The cough refiex ismost sensitive in the trachea and larger airways. The sensitivityprogressively decreases in the finer airways and in the very fineairways there is no refiex at all. So in alveolitis, there is littlestimulation of the cough reflex, whereas for tracheitis thestimulus is strong). By clearing abnormal mucus or by changingits character and making it more demulcent, expectorants canallay cough and are therefore antitussive.

Classification of Expectorants (after Gunn, 1927)The classification of expectorants by their mode of action is

extremely valuable in understanding their appropriate use. In1927 Gunn proposed four classes of expectorants.^ A fifth classwas suggested by the Russian scientist CJordonoff.̂

L Reflex expectorantsThese are emetics which cause an increased secretion of

respiratory tract fluid when given orally in subemetic doses. Actby reflex from the upper GIT mediated by the vagus nerve egsaponin herbs, Lobelia, Ipecac

2. Central expectorantsAct on the CNS. Possibly Ipecac

3. ParasympaticomimeticsStimulate the vagus nerve eg Pilocarpus. Also capsaicin (in

Capsicum) stimulates bronchial C-fibres

4. Stimulants of secretory cellsAct directly on goblet cells, eg essential oils

5. Secretomotorics (after Gordonoff 1938)Stimulate mucociliary transport, eg camphor, thyme

From the herbal perspective the two most important classesare the refiex expectorants and the stimulants of secretory cells.The use of the terms stimulating or relaxing expectorants is nolonger valuable, as the following quotation illustrates.

"EXPECTORANTS may be defined as drugs which promotethe expulsion of secretion or exudates from the respiratory

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passages, or which modify their characters. They were formerlyclassified into stimulating and depressing groups, the formerbeing supposed to increase blood pressure and diminish secretion,the latter to lower blood pressure, increase secretion and promoteexpulsion. These terms are now generally discarded."^

Reflex ExpectorantsThere is no doubt that emetics can induce a powerful

expectorant effect, as highlighted in the following quotation: "Itis safe to assume that even in remote times physicians soughtfor drugs that would facilitate or increase the flow of bronchialsecretion. Almost inevitably they tried to imitate the phenomenonwhich is known to accompany bouts of nausea when both salivaryand the bronchial secretions are noticeably increased by thespread of stimuli from an overactive vagus to the secretory nerveendings in the respiratory tract....

"...The method still finds practical application in themanagement of non-diphtheritic croupy cough of young children:a substantial emetic dose of tincture of ipecacuanha isadministered on a fasting stomach; within ten minutes the childturns pale...and vomits or retches several times. The emeticaction is accompanied by an outpouring of hronchial mucus whichis removed by more or less violent coughing.. .such treatment.. .isundoubtedly effective in clearing stringy, tenacious mucus fromthe trachea and larger bronchi, and may give striking relief ...."^

However, the critical question is whether emetics in suhemeticdoses can still provide a clinically relevant expectorant effect.This issue was researched in the 1940s hy the Canadian scientistBoyd, who used several experimental models."̂ ^ He was able toshow that both saponin-containing herhs (such as Polygalasenega), which can act as gastric irritants, and ipecac exertedexpectorant activity at subemetic doses (as measured hy anincrease in respiratory tract nuid).^^The effect was eliminatedif the efferent gastric nerves were cut.

Secretory Cell StimulantsEssential oils from various herbs (either administered as

essential oils or contained in herbal extracts or tinctures) arethe most important agents which directly influence gohlet cellsto secrete more respiratory tract fluid (RTF) and mucus. AgainBoyd studied the effects of several essential oils in variousexperimental models.^'^ The most pronounced increase ofrespiratory tract fluid was seen after ingestion of oil of anise.Interestingly, ingestion of oil of eucalyptus had a moderate effectwhich was not eliminated by cutting efferent gastric nerves. Thisfinding supports the premise that essential oils do not act asreflex expectorants.

One fascinating aspect of Boyd's research is that he was ableto demonstrate that inhaled essential oils also acted asexpectorants. These results are summarized in Table 1.

Table 1 - Expectorant Effect of Inhaled Essential Oilsor Their Components

Year of ExpectorantsStudy Studied Results IRTF = Respiratory Tract Fluidl

1968* Thiya oil RTF markedly increased, as was the solublemucin content of RTF. Effect was mostmarked in fall

Anise oil No effect at normal doses

Eucalyptus oil No effect at normal doses

1969" Menthol No change in amount of RTF, but its soluble

mucin content was increased

Thymol No effect at normal doses

1970'" Lemon oil RTF and its soluble mucin content increased

1970" Nutmeg oil RTF and its soluble mucin contentmoderately increased. Effect moatpronounced in fall

1970'̂ Citral, geraniol RTF and its soluble mucin contentmoderately increased

Lower Respiratory Disease

Boyd found a biphasic effect in that high concentrations ofessential oils suppressed RTF and mucin release, whereas lowerdoses (on the threshold of detection by the nose) had a pronouncedstimulatory effect. A seasonal effect was also observed, with anincreased activity in fall. These findings provide a rational basisfor the hot lemon drink in respiratory infections, since activeamounts of lemon oil would be inhaled while ingesting the hotdrink.

Overview of Expectorants• An expectorant is a substance which enhances those

physiological mechanisms by wbich respiratory tractsecretions are cleared from the lungs. In the course of doingthis they often render the consistency of respiratory tractsecretions more fluid and/or more demulcent. They do notnecessarily increase the quantity of coughed-up phlegm, norare they necessarily antitussive.

• Since reflex expectorants and stimulants of respiratory tractsecretory cells act by different mechanisms, and on differentparts of the lung tissue, an effective herhal prescription shouldprobably combine these two types of expectorants, dependingon the patient's condition.

• The effect and mechanism of action of reflex expectorantshas been demonstrated by scientific experiments. However,since their effect seems to involve vagal stimulation ofsecretory glands, there may also be vagal stimulation ofsmooth muscle tissue in the lungs. Hence they should be usedwith caution in asthma, and combined with hronchiolarspasmolytics, but not anticholinergics.

• Many lower respiratory tract disorders will benefit from theaction of expectorants, but particularly those where mucusis tenacious and difficult to cough up. However, it dependson the cause of a cough whether an expectorant action is alsoantitussive.

• Agents with expectorant activity may have other actions, forexample some inhaled terpenes may be spasmolytic forhronchiolar smooth muscle.

• Based on animal experiments, oil of anise (and fennel)appears to be a good expectorant when given orally. Theexpectorant action of inhaled essential oils should not beunderestimated. Particularly effective are the lemon-scentedterpenes.

• Although the scientific research supporting the therapeuticaction of expectorants is by no means conclusive, there isinsufficient objective justification for statements like, "Thereis little evidence to show that expectorants are effective."

• Key reflex expectorant herhs are Polygala and Lobelia (butmany saponin-containing herbs will also have this property).Expectorants which are stimulants of secretory cells probably

include anise iPimpinella anisum), thyme (Thymus vulgaris),fennel (Foeniculum vulgare) and white horehound {Marrubiumvulgare).

AnticatarrhalsAnticatarrhal herbs have the following beneficial properties:

they reduce excessive discharge from mucous membranes. Thisdischarge may vary from clear and thin to thick and yellowishdepending on the condition. They decrease airwayshypersensitivity and can also decrease nasal congestion andmucosa] edema. Anticatarrhal herbs for the upper respiratorytract include eyehright lEuphrasia officinalis), ribwort (Plantagolanceolata), Ephedra [Ephedra species), elderflower {Sambucusnigra), peppermint iMentha x piperita), ground ivy (Glechoma

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Lower Respiratory Disease

hederacea, Nepeta hederacea) and goldenseal (Hydrastiscanadensis). Goldenseal {H. canadensis) is particularly indicatedwhere there is copious yellow to green discharge of a chronicnature. Goldenrod (Solidago virgaurea) may also fit into thiscategory. Anticatarrhal herhs for the lower respiratory tractinclude mullein (Verbascum thapsus), Ephedra (Ephedra species)and ribwort (P lanceolata).

The mode of action of these herbs is not fully understood,especially the herbs rich in the phytochemicals known as iridoids.These include eyehright, ribwort, ground ivy and mullein. Giventhat so many anticatarrhal herbs contain iridoids, the propertiesof these compounds are worthy of further investigation in thiscontext.

Respiratory DemulcentsThese herbs are rich in mucilage and have a soothing and

antiinflammatory action on the lower respiratory tract. Mucilagesare generally not chemically well-defined. They are large highly-branched polymeric structures built from many different sugarand uronic acid units (uronic acids are carboxylic acids derivedfrom sugars). They are very hydrophilic (water-loving) and arecapable of trapping water (and other molecules) in their cage-like structures to form a gel. Consequently, when a mucilage ismixed with water it swells to many times its original volume asit absorbs water. The saccharide linkages are in a hetaconfiguration which means that human digestive enzymes cannotbreak down mucilages. Although the mechanism behind reflexdemulcency is not clear, an opposite effect to that of the reflexexpectorants has been postulated; ie the effect is a reflex onefrom the demulcent effect on the upper digestive tract, againinvolving common embryonic origins and vagal innervation.

The major respiratory demulcent herbs are Althaea officinalis(marsbmallow root or leaves) and other members of theMalvaceae (mallows), Ulmus spp (slippery elm), members of thePlantago genus, Cetraria islandica (Iceland moss) and Chondruscrispus (Irish moss). Tussilago (coltsfoot) and Symphytum(comfrey) were very widely popular before concerns aboutpyrrolizidine alkaloids constrained their use. Pronouncedantitussive activity has been demonstrated experimentally withoral doses of 1000 mg/kg hody weight of extract of Althaeaofficinalis (marshmallow), with comparable effects at 50 mg/kgof the isolated mucilage."

Respiratory demulcents were popular for children's cough andgenerally for dry, irritable and ticklish coughing. Reflexdemulcents are doubly indicated for asthma if it has been linkedto esophageal reflux of gastric acid. Here the demulcencyadditionally allays the irritating effects of acid in the esophaguson the lungs, which is also possibly mediated hy a similar vagalreflex to reflex expectoration. A recent paper reported theinvestigation into the link between acid reflux into the esophagusand coughing or wheezing fits in asthmatic patients.''' Thescientists asked a question which has been debated for some timeamong respiratory and gastrointestinal physicians: "Does coughcause reflux or does reflux cause cough?" They studied more than100 chronic adult asthmatics and found that half of al! theircoughs and wheezes occur at the same time as when acid refluxesfrom the stomach into the esophagus. But more importantly theyconcluded that in the majority of cases it was the reflux whichcaused the coughing and not the other way around. The scientistssuggested that the potential of antireflux therapy in thetreatment of asthma needs to be studied further.

This link between reflux and asthma has long been suspected.In fact there is evidence that reflux is an important cause ofasthma in some asthmatics. Monitoring of esophageal acidityrevealed reflux in 7 out of 9 patients with persistent asthma.^^Inanother study 61%of patients with asthma had reflux."^ Fromstudies on children it was concluded that asthma symptoms weremore often elicited by exposure of the esophagus to gastric acidthan by aspiration of gastric juice.'' However other studies haveimplicated the importance of acid aspiration."*'^

The chronic cough which often follows a respiratory infectionand seems to persist long after the infection is gone is probablydue to acid reflux, which in turn was induced by the weakeningof the esophageal sphincter as a result of the violent coughingduring the infection. A true viscous cycle! Here the role of reflexdemulcents is again particularly valuable.

The old-fashioned cough syrups were hased on the principleof reflex demulcency. The syrup was not only soothing to thethroat, but also relieved coughing coming from the lungs or fromesopbageal reflux by its demulcent effects.

ConctusionsThe use of expectorants, anticatarrhal and respiratory

demulcent herbs comprises a key aspect of phytotherapy fordiseases of the lower respiratory tract. When these herbs arecombined, as appropriate, with those with other actions such asrespiratory spasmolytics and antiseptics, a rational approach tothe management of both acute and chronic respiratory diseasecan be developed.

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