Asthma 2014 Edition · 2019. 4. 25. · asthma. In this edition of the newsletter we focus on...

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Volume 5 No 3 - August 2014

Asthma 2014 Edition

2 Volume 5 No 3 - August 2014

lobally, asthma is the commonest chronic childhood illness with over 300 million cases reported annually. In South Africa it is responsible for 4th highest disability adjusted life years in terms of morbidity. In the recent South African study on asthma-related morbidity, only about a quarter of

cases with symptoms suggestive of asthma were on medications for the condition. Worst still was that the majority of these cases were not on anti-inflammatory therapy and only 6-8% on those on anti-inflammatory therapy was well controlled. Current evidence from the literature clearly shows that there are effective preventative and

treatment options for children with asthma. So why are we failing to control childhood asthma. In this edition of the newsletter we focus on improving knowledge and clinical practice associated with childhood asthma.

We are indeed blessed to have five excellent articles to improve knowledge and practice around childhood asthma. Firstly, we have a manuscript describing ‘Asthma as an inhomogeneous disease with different phenotypes’, then we have presentation on the latest information on ‘Allergy and asthma prevention strategies in childhood’ which is followed by an article on ‘The use of a peak flow meter in clinical practice’. Finally, we

end with 2 important contributions on the ‘Practical evidence-based advice to assess the control of asthma in children and the association of ‘Asthma

and pneumococcal disease’.

These publications provide the latest information on the various sections of childhood asthma and are prepared by Members of the National Asthma Education Program and experts in the

field. My sincere thanks goes to these authors who have gone the ‘extra mile’ to further asthma education to health care workers and

patients/caregivers.

I trust that you will find this newsletter useful to your daily practice so that we can curb the morbidity associated with this disease. While asthma is non curable, there is Grade A evidence that the disease can be prevented and effectively treated. The challenge is with us, healthcare

professionals to diagnose and manage these children with asthma effectively so that they can realise their dreams of a

fully accomplished life.

God Bless

Professor PM JeenaChief Editor

Editorial

Can we reduce the morbidity associated with childhood Asthma?

Associate Professor Prakash Mohan JeenaHead of Paediatric Pulmonology and Critical CareUniversity of KwaZulu NatalDurban

Professor PM Jeena

The views expressed by the editor or authors in this newsletter do not necessarily reflect those of the sponsors or publishers.

Sponsor: PfizerEditor: Prof Prakash Mohan JeenaProduction Editors: Ann Lake, Helen Gonçalves Design: Jane Gouveia Queries: Ann Lake Publications 011 802 8847Website: www.annlakepublications.co.zaEmail: [email protected]

Request for contributionsWe welcome submissions of articles from paediatricians, GPs with a special interest in paediatrics and academics etc. for publication in this newsletter. Please email articles to: [email protected]

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Doctors can acquire CPD points with this newsletter by visiting www.paediatrician.co.za, www.mycpd.co.za, www.pandasa.co.za or www.annlakecpd.co.za and completing an online form of questions. Doctors whose articles are published in this newsletter will also automatically be awarded CPD points. Accreditation is available only for a limited time on the site. Should you have any queries regarding the accreditation, please contact E2 Solutions at: 011 340 9100 or [email protected]

3Volume 5 No 3 - August 2014

sthma is a chronic inflammatory disorder of the airways. Inflammation in asthma leads to airway hyper-responsiveness in response to triggers, reversible

obstruction and clinical symptoms.1 According to International Study of Asthma and Allergy in Childhood(ISAAC phase 3), the global the prevalence for current asthma in the 13-14-year age group is 14.1%, In the 6-7-year age group the prevalence for current asthma, is 11.7%.2 The GINA report estimates 300 million asthma sufferers globally with further estimated additional 100 million sufferers by 2025.3 Current reports on the global burden of diseases in terms of Disability adjusted life years(DALYs) ranks asthma as the fourth commonest respiratory burden in children aged 10-14 years.4

One of the biggest challenges is that asthma is a heterogeneous disease with different phenotypes and understanding the pathophysiological mechanism of each phenotype will assist in improvement in management and ultimately achieving asthma control thus reducing the burden of the diease.

Pathophysiology of asthmaCentral to pathophysiology of asthma is airway inflammation. A foreign substance (virus or al-lergen) once in contact with the airway is recog-nised by an antigen presenting cell on the air-way epithelium (Langerhans cell, Dendritic cell). This cell will present the engulfed substance to the lymph node. This results in a cascade of im-mune system stimulation resulting in inflamma-tory cells such as eosinophils, neutophils and granulocytes infiltrating the airway wall leading to bronchial hyper-responsiveness and possibly airway remodeling.5 These cells are recruited from the pleuro-potent stem cells in the bone marrow. Eosinophils adhere to endothelial wall assisted by adhesion molecules and vascular cell adhesion molecule 1(VCAM 1). Eosinophils are assisted by chemokines to enter the site of inflammation and release eosinophil cation pro-

tein, peroxidases, protein X and free acid rad-icals.5 GM-CSF and IFN-y attract Neutrophils to the site of inflammation. This result in release of elastases and subsequent hyper secretion and hyper reactivity of the airway. With the release of Matrix Metalloproteinase 9 there is collagen breakdown, release of oxygen free radicals and bronchial hyperresponsivenes.5,6 In addition there are other host and environmental factors like pollen, house dust mite and animal dander, air pollution, exercise, drugs (aspirin and beta blockers), emotional expression like crying and laughing and environmental tobacco smoke that contribute to the pathophysiology of asthma.

Airway remodeling is a histological diagnosis characterised by bronchial epithelial damage, thickening of reticular basement membrane, sub-epithelial fibrosis and mucus gland and airway smooth muscle hypertrophy and hyperplasia. These structural wall changes result in decrease in lung function.5,7,8

Whether airway remodeling represents chronic inflammation or not is still a matter of debate. There is evidence from airway biopsy studies in children that the histological features

Asthma is not a Homogenous Disease - Different asthma phenotypes and their impact on managementDr Omolemo P Kitchin. MBChB, FCPaed, MMed(Paed), Dip. Allerg(SA), Cert Pulm(SA)Paed, FCCPPaediatric PulmonologistWaterfall City hospital, Midrand, Johannesburg

described above can be found early asthmatics before symptoms occur.9,10 Figure 1

Even though this pathophysiology looks sim-ple, the reality is that there is no one size fits all in asthma. Genetics have revolutionised the understanding and pathophysiology of asthma. Genome wide association studies (GWAS) per-mits a comprehensive search of the genome with a possibility of identifying novel genetic factors for disease development.11 Due to its high sen-sitivity and the ability to localize to a small area on a chromosome, it provides opportunity for targeted genes identification which will aid in possibly identifying pathophysiological biomark-ers and possibly treatment. This GWAS is a great opportunity for proper classification of asthma phenotypes. One of the current concepts related to GWAS is epistasis. Epistasis is defined as inter-action between multiple different genes affecting phenotypes.11 Asthma being a heterogeneous disease allows analysis of interaction between 2 genes capable of creating a phenotype for exam-ple, interaction between Cytokine–IL4Ra and cy-tokine associated receptor IL13 has been linked with physician diagnosed asthma.11

Figure 1. Adapted from Recent Advances in the Pathophysiology of Asthma. Desmond M. Murphy, MB , PhD ; and Paul M. O’Byrne , MB , FCCP. CHEST 2010; 137(6):1417–1426

Remodeled and inflamed airway

Airway lumenEpithelium

Lamina Propria

Smooth Muscle

Systemic Processes


1. Pre-asthma wheezing phenotypePresentations vary. Episodic wheezing phenotype presents as episodes of wheezing only during viral respiratory tract infection and then remit. In multi-trigger wheeze, patients wheeze during and apart from respiratory tract infection. They respond to inhaled corticosteroids.13 Other phenotypes of pre-asthma wheezing include early transient wheeze, where episodes occur only in the first 3 years of life and then remit. In persistent wheeze, children wheeze in the first 3 years of life but persist into school age (closely related to non-atopic asthma).13 These groups do not demonstrate significant association with atopy, but an association with decreases in FEV1, FEF (25-75) levels, airway hyperactivity at 7-8 years and maternal asthma and smoking has been demonstrated.12 Late onset wheezers, have minimal symptoms in the first 3 years of life with wheezing becoming prominent after 6 years of age. These patients are likely to have a positive skin prick test, chronic rhinitis and maternal asthma without significant elevated IgE levels.12

2. Atopic phenotypeAtopic asthmatics have evidence of a positive skin prick test and of elevated IgE levels. They are usually steroid responsive, have higher FEV1 levels, are closely associated with chronic rhinitis co-morbidity and are usually young. They account for more than 50% of asthmatics.12 Non-atopic asthmatics demonstrate the opposite in that there is no evidence of positive skin prick test and elevated IgE, are older, and have a more

severe disease. The triggers include infection, irritants stress, inflammatory cells.12 These clearly demonstrate an overlap between phenotypes.

3. Inflammatory phenotypeEosinophilic asthma is the more common type with good response to corticosteroids and bronchodilators but associated with frequent flares.12,15

Neutrophil asthma is closely linked to endotoxins, infections and irritants. These patients demonstrate increase in Leukotrine B4 in BAL and IL-8. May respond to macrolides but poorly responsive to steroids.12,16

4. Exercise induced asthma phenotypeIt is defined as a condition in which exercise induces cough, bronchospam and tight chest in patients with asthma.17 These symptoms are accompanied by a reversible drop in FEV1 of 10-20%. Prophylactic beta agonist given 10-15 minutes before exercise can reduce symptoms.12,17

5. Aspirin sensitive asthma phenotypeThis phenotype is commonly described in Samter’s triad-nasal polyposis, aspirin sensitivity and asthma.12,18 Prevalance of Aspirin sensitivity from the TENOR (The Epidemiology and Natural History of Asthma: Outcomes and treatment Regiment) study was reported to be 14%.18 These patients are usually adult females having lower FEV1, more severe asthma and non-IgE induced symptoms.

They have high urinary leukotriene E4. Management includes leukotriene antagonists, nasal polypectomy(surgical removal of nasal polyps) and intranasal topical steroids.12,18,19

6. Severe asthma phenotypeThis constitutes less than 10% of all asthmatics but contributes to up to 40% of the economic burden of treating asthmatics.12,15 They are also often classified as refractory asthma, difficult to control asthma, steroid resistant asthma, poorly controlled asthma and brittle asthma.20

Management includes ruling out conditions that mimic asthma and result in poor control i.e. gastro-oesophageal reflux disease, vocal cord dysfunction, environmental tobacco smoke exposure and rhinitis co-morbidity.21 If they are truly steroids resistant, a trial of boutique therapies of unconfirmed benefit in children i.e. Anti IgE (Omalizumab), Anti-IL5 (mepolizumab, Anti-TNFalpha (Golimumab) and Bronchial thermoplasty may be attempted.

7. Flare-up prone asthma phenotypeThese patients are often poorly controlled and have frequent Emergency Room visits and hospitalisation.22 Risk factors include recurrent infections (rhinovirus infection), allergen exposure, female sex and previous flares.

8. Obese non-eosinophilic phenotypeThis phenotype is usually seen in adolescents and adult women.14 Leptins and adipokines are thought to be important mediators in airway disease with a direct effect on airway.14,23

Management includes weight loss, hormonal therapy antioxidants.14

ConclusionEnormous strides have been made in host ge-netics to better describe the pathophysiology of asthma. New information on genetics and epistasis is encouraging. Attempts at classify-ing asthma based on phenotypes have been developed, although there is a lot of overlap between phenotypes. More work is required to better explain the phenotypic pathophysiolo-gy of this heterogenous disease with a hope of finding phenotype specific targeted thera-py. This will assist in re-inforcing the ultimate goal in management of chronic asthma, that is achieving asthma control. Patient education is key to realizing this dream.

References available on request.

Classification of Asthma phenotypes.12,13,14

Phenotype Example

Pre-asthma wheezing Episodic wheeze/Exclusive viral wheeze

Multitrigger wheeze

Early transient/Persistent/Late onset wheeze

Atopy Atopic

Non-atopic

Inflammatory Eosinophilic

Neutrophilic

Pauci-granulocytic

Exercise induced asthma

Aspirin sensitive asthma

Severe Asthma Refractory/Difficult asthma

Flare prone asthma

Obese non-eosinophilic


Figure 1: The ‘window of opportunity’ to induce allergen tolerance

An overview on allergy and asthma prevention strategies in childhoodProfessor Samuel Malamulele Risenga BSc (Unin), MB CHB (Natal), DCH, Dip Allergology (SA), MMed (Medunsa) Paed, Cert Pulmonology (SA) (Paed), FAAAAIHead of Clinical Department and Associate Professor, Paediatric Pulmonology and Allergy,University of Limpopo, Polokwane Campus, South Africa

llergy and asthma are a growing public health and clinical problems worldwide.1,2 In many countries, the prevalence of both conditions has demonstrated a rapid increase

in recent decades, occurring most commonly among young people.2 In western societies, there has been a doubling in the prevalence of allergic conditions every 15 years, over the last 50 years.3 Both allergic disorders and asthma have a major effect on the quality of life of children and adult sufferers as well as their families. It can lead to poor performance and productivity at school and work.

The development of asthma and allergy probably follows on interplay between an individual’s genetic makeup and their environment. In particular asthma, atopic dermatitis, food allergies and allergic rhinitis are products of an excessive and inappropriate immune response to environmental antigens and the consequent inflammation that follows.2

Due to the enormity of the allergy and asthma epidemic, there has been a worldwide drive to investigate mechanisms to prevent these conditions. This article will discuss these strategies and suggest evidence-based tools that may be employed.

Does timing of solid food introduction to an infant diet matter in allergy prevention?The prevalence of IgE-mediated food allergy has increased in the last 20 to 25 years.4 Since 1990, this increase has been coupled with an increase in hospitalisation due to food allergy-related anaphylaxis and other serious life-threatening manifestations of food allergy in the United Kingdom.4

In the past, guidelines have recommended a delay in the introduction of allergenic foods

to infants with a family history of allergy, in-cluding avoidance of eggs until 2 years of age and nuts until 3 years of age.4 Present-ly the World Health Organization strategy to prevent allergy, is promotion of exclusive breast-feeding for the first 6 months of life, and delaying weaning to solids and milk for-mulas until after 6 months of age.5 There is, however, no convincing evidence for the protective effect of exclusive breast-feed-ing beyond 4 months of age.5 Nwaru et al, however, reported that a longer duration of exclusive breast-feeding was protective against the development of non-atopic asth-ma.6 This suggests a potential discordant effect of breast-feeding on the development of different asthma phenotypes.6 Prolonged breast-feeding is, however, encouraged be-cause it is the safest way of feeding in poorly resourced countries.

Despite the lack of population studies that have directly investigated the relationship between infant weaning in the first year of life and risk of confirmed food allergy, the timing of first exposure has been dramatically delayed over the last few decades. Until the 1970’s, most infants had been exposed to solids by 4 months, between 1970 and 1990 after 4 months and after 6 months of age by the late 1990’s.4 Despite these changes, there has been an acceleration of food allergies, raising the possibility that delay in the timing of introduction of solids is not protective against food allergies, and might actively contribute to the increasing prevalence of food allergies.4

The American Academy of Pediatrics had previously advised that there should be no maternal dietary restrictions, with the exception of peanut during pregnancy.1

Koplin et al. have shown, in their population-based egg allergy prevention study, that infants exposed to cooked egg between 4 to 6 months of age had a lower risk of developing egg allergy. They also postulate that their finding was in keeping with the new concept of a ‘window of opportunity’, during which exposure to potentially allergenic foods promotes the development of oral tolerance.4 Nwaru et al. also reported that early introduction of wheat, rye, oats, barley cereals, fish and egg seems to decrease the risk of asthma, allergic rhinitis and atopic sensitization in infancy and childhood.6

In a prospective pre-birth cohort study of participants unselected for the propensity for atopy, Bunyavanich et al found that higher maternal intakes of allergenic foods during early pregnancy were associated with lower risk of allergy and asthma in mid-childhood.1 This intrauterine exposure to allergenic foods may play a role in the protection against the development of allergy and asthma by immune intolerance since the immune system is shaped during the foetal period.1 It is therefore appropriate to target this period in the quest to decrease asthma and allergies. See Figure 1 for window of opportunity to induce allergen tolerance.

Birth 3-4 months 6-7 months >12 months

High risk Window High risk Resolution

Tolerance induction


Allergies, infections and the Hygiene HypothesisThe Hygiene Hypothesis proposes that early childhood exposure to infectious agents, gut flora, and parasites decreases susceptibility to allergic diseases by modulating immune system development.5

The first suggestion that infection and unhygienic contact may confer protection from development of allergic diseases was made by David Strachan in 1989, with a large number of population-based studies confirming an inverse association between the number of siblings and the development of allergic outcomes.7 The Hygiene Hypothesis is based on the T helper cell type 1 and T helper cell type 2 (TH1/TH2) balance controlled by T regulatory cells which secrete IL-10. This process leads to allergen-specific, protective, IgG4 formation.3

According to epidemiological studies over the last decades, the Hygiene Hypothesis has been recognized as a complex interplay of many factors rather than a single factor affecting the TH1/2 balance.7 There are four factors that are related to the Hygiene Hypothesis viz. the various allergic diseases (including the different phenotypes), timing of exposure, various environmental exposures and the individual genetic susceptibility.7

There are different wheezing phenotypes in childhood asthma, such as episodic wheeze, multi-trigger wheeze, transient wheeze (which remits around the second and third year of life) and other forms of wheezing which persists, especially the allergic wheezing phenotype. The timing of various exposure to allergens potentially relates to the Hygiene Hypothesis and asthma. Studies have shown that allergen exposure during the development and maturation of the immune system in childhood, adolescence and prenatally may play a role in the subsequent development of allergies.5

Vitamin D and asthma in childrenAsthma is driven by increased activity of TH2 cells by inducing IgE production and the promotion of eosinophilic airway inflammation and hyperresponsiveness. Vitamin D has been shown in mouse and human models to inhibit T cell proliferation and TH1 responses, and recently, the reduction of TH17 responses.10 Vitamin D has been shown to enhance the production of IL-10 in human studies. IL-10 is an anti-inflammatory cytokine.7 Data from epidemiological studies has suggested that, in asthmatic children, where serum vitamin D levels are insufficient, asthma symptoms and exacerbations occur more frequently.10

These observational studies have not proven causality despite the suggested association of vitamin D insufficiency and asthma.10

Although studies suggest a role for vitamin D in asthma control, there have been other studies suggesting that the vitamin D given in excess, may promote the asthma phenotype.7 Some authors have suggested that regular vitamin D supplementation of 2000IU/day, given in the first year of life increased the risk of atopy and asthma development when these individuals were assessed for asthma at 31 years of age.This study had a methodological flaw as there was limited data on vitamin D maternal intake and assessment of children for atopy or asthma.10

There is quality epidemiologic and immunologic data suggesting that both vitamin D excess and deficiency may result in increased risk of allergy development.5

Furthermore long-term, multicentre randomized trials are required to document the ideal dose of vitamin D supplementation for asthma and allergy prevention and treatment.10

Antioxidant supplements and nutrientsThere is normally a balance between reactive oxygen species and antioxidants in a healthy human body. The imbalance

The genetic potential of an individual is subject to a number of environmental influences at various points in the developmental period. These interactions contribute to the mechanisms that underlie the various allergic conditions.7

Factors that have been associated with a reduction in the prevalence of IgE-mediated allergic diseases are increased family size, birth order, growing up on a farm and visits to day care centres. The exact immunological mechanisms underlying the Hygiene Hypothesis have not been fully elucidated, but one of the postulates is the reduced immune regulation caused by reduced infection stress. The decrease in infection stress further decreases the counter-regulatory role of IL-10 dependent on infections.3

Vaccination as a protective strategyIn a multicentre German birth cohort study that followed children from birth to 20 years of life, Grabenhenrich et al. were able to show that vaccination appears to play a role in the prevention of allergy and asthma. Their previous analysis of children who started school in 1994, had shown a lower risk of allergy and asthma in children who were vaccinated against measles, mumps and rubella (MMR) as well as for BCG by 5 years of age.8

Their current analyses revealed that the protective effect against asthma appears to last until adulthood in participants that received certain whole-organism vaccines viz. MMR, BCG and tick-borne encephalitis in early childhood compared to those who did not receive them.8 They were, however, unable to examine the effect of other vaccinations.8 On the other hand, Linehan et al in their Manchester Community Asthma Study, found evidence that any protective effect of BCG vaccination in childhood asthma was probably transient.9 These conflicting findings might be due to the fact that the German study did not study BCG vaccination only.8


between antioxidants and pro-oxidant defences is known as oxidative stress. This oxidative stress might increase skewing of the TH1/TH2 cytokine production towards a TH2 dominant profile. This is associated with the development of allergic diseases.2 Pulmonary and systemic oxidative stress increases inflammatory responses that are relevant to the development and control of asthma and allergy.11 The human body has endogenous antioxidants produced through enzymatic processes within cells.2 Exogenous antioxidants are vitamins β-carotene, A, C and E, with vitamin C being the most abundant antioxidant in the extracellular fluid that lines the lungs.2

Additional trace element antioxidants are selenium and zinc. Meta-analyses have revealed a significant association between low dietary intake of vitamin A and C and higher rates of asthma and wheezing, while high vitamin E intake during pregnancy reduced the risk for wheezing in children by 32%.2

It is still not known how antioxidants in the diet or dietary supplements might be used to control or prevent asthma and allergy development.2

Prebiotics and ProbioticsPrebiotics are non-digestible fermentable oligosaccharides which accelerate growth of beneficial microbial organisms in the gastrointestinal system. On the other hand probiotics are living microorganisms which exer t health benefits beyond inherent general nutrition. There is evidence, limited mainly to lactobacilli and bifidobacteria, that they induce systemic immune regulatory mechanisms. They preferentially elicit two substantial T cell lineages, which counterbalance the predominance of the pro-allergic TH2 directed immune response.12 There are conflicting repor ts on the role of probiotics in decreasing respiratory allergy, IgE levels, allergic sensitisation and asthma development. Currently, there is no reliable data to recommend or reject probiotics/prebiotics for prevention of respiratory

allergy.12 Despite great expectations; the general agreement is that additional trials are still needed in this regard.12

ConclusionPrevention of asthma and allergic disease is a complex and challenging process. It needs a thorough understanding of the interplay between the genetic makeup (not discussed in great depth in this article) of individuals and the environment. Great strides have been made with attention presently directed to prevention of exacerbations and changing dynamics of disease progression in asthma and allergic disease.6

AcknowledgementsI would like to acknowledge the following people for their help and encouragement in the preparation of this article:

• Professor Robin Green head of the Depar tment of Paediatrics and Child Health at the University of Pretoria who is my teacher and continues to mentor me. He played a major role in the reviewing of this ar ticle and gave me valuable suggestions.

• Dr Ntshengedzeni Maligavhada, who is the first paediatric pulmonologist I trained at the University of Limpopo, Polokwane Campus. She helped me with the drawing of the figure on ‘Window of opportunity ‘in this ar ticle.

• Dr Aletta Motene, one of my fellows in training in paediatric pulmonology.

• Mrs. Tlou Ndou, my personal assistant who supports me a lot in my office work.

References1. Bunyavanich S, Rifas-Shiman SL, Platts-

Mills TA, et al. Peanut, milk, and wheat intake during pregnancy is associated with reduced allergy and asthma in children. J Allergy Clin Immunol 2014; 133:1373-82.

2. Moreno-Macias H, Romieu I. Effects of antioxidant supplements and nutrients on patients with asthma and allergies. J Allergy Clin Immunol 2014; 133:1237-44.

3. Joost van Neerven RJ, Knol EF, Savelkoul HFJ. Which factors in cow’s milk contribute to protection against allergies? J Allergy Clin Immunol 2012; 130:853-8.

4. Koplin JJ, Osborne NJ, Wake M,et al. Can early introduction of egg prevent allergy in infants? A population-based study. J Allergy Clin Immunol 2010; 126:807-13.

5. Boyce JA, Finkelman F, Shearer WT, et al. Update on risk factors for food allergy. J Allergy Clin Immunol 2012; 129:1187-97.

6. Szefler SJ. Advances in pediatric asthma in 2013: Coordinating asthma care. J Allergy Clin Immunol 2014; 133:654-61.

7. Mutius E. Allergies, infections and the hygiene hypothesis-The epidemiological evidence. Immunobiology 2007; 212:433-439.

8. Grabenhenrich LB, Gough H, Reich A, et al. Early determinants of asthma from birth to age 20 years: A German birth cohort study. J Allergy Clin Immunol 2014; 133:978-88.

9. Linehan MF, Nurmatov U, Frank TL, et al. Does BCG vaccination protect against childhood asthma? Final results from the Manchester Community Asthma Study retrospective cohort study and updated systemic review and meta-analysis. J Allergy Clin Immunol 2014; 133:688-95.

10. Gupta A, Bush A, Hawrylowicz C, et al. Vitamin D and asthma in children. Paediatr Respir Review 2012; 13:236-243.

11. Ober C, Yao TC. The genetics of asthma and allergic disease: a 21st century perspective. Immunol Rev 2011; 241: 10-30.

12. Feleszko W, Jaworska J. Prebiotics and probiotics for the prevention or treatment of allergic asthma. London,UK:Elsevier inc. 2010


sthma, which from its Greek origin means ‘to pant’, is a chronic inflammatory and hypersensitivity condition of the airways. It is characterised by variable and

recurring symptoms of airway obstruction which is partially or fully reversible. The most common symptoms of asthma include coughing, shortness of breath and wheezing. Patients might experience all of these symptoms at varying degrees and stages, or they may have one symptom more characteristic to them.

To aid in the diagnosis there are several useful objective measures that we can use to measure airway obstruction; methacholine challenge, steroid response test, spirometory test and the peak flow meter test. In this article I discuss the use of a peak flow meter in a clinical practice.

What is a peak flow meter? The peak flow meter is an important and inexpensive hand held device, which is a useful tool in diagnosing asthma and for gaining and maintaining control of the condition. It helps to determine the level of obstruction of airflow through the large airways by assessing how much air can be forcibly exhaled after maximum inhalation i.e. peak expiratory flow, PEF, or peak expiratory flow rate, PEFR. It is measured in litres per second l/sec.

Dr. B.M. Wright created the first peak flow meter in the late 1950s. A smaller more portable adaptation of the original, the Mini Wright meter, (see fig 1) is most commonly used today. It consists of a cylindrical body, and a removable and cleanable mouthpiece. On the body of the peak flow is a scale – litres per second – and a cursor, which ‘shoots’ forward along the scale during a test or ‘blow’ and that can be returned to zero after each attempt. Some peak flow meters designed for personal asthma management have a cursor indicating

The use of a peak flow meter in clinical practice

Heidi Facey-Thomas, RN, dip Asthma (NAEP), Cert. Professional Allergy Nursing, UNISAAllergy Department, Red Cross Children’s Hospital, Rondebosch, Cape Town, South Africa

the desired measurement for that patient as well as an additional indicator which can be pre-set to indicate when a reading is too low and action needs to be taken. These indicators are usually red when action needs to be taken. Most peak flow meters can be fitted with disposable cardboard mouthpieces and these are more desirable to use in a busy clinic. Although there are several makes of peak flow meters they essentially fall into two types: low range peak flows and the standard range peak flow. The low range peak flow is for younger children and those with severe asthma and a compromised lung function. The standard range meter is for older children and adults. Peak flow meters should be renewed every two years and the mouthpiece, if not disposable should be cleaned with warm soapy water between uses. Who can use a peak flow meter?The standard answer to this question is; anyone five or older. However, there are very few five year olds who can use the peak flow meter correctly. Therefore, a better response would be anyone who has the co-ordination and understanding of what it entails to blow into a peak flow meter and who can reproduce the test within a discrepancy of less than 5-10%. This might well be a five-year-old child, but there are many adults who have not got the co-ordination to use it correctly. It is up to the clinician to decide whether or not the technique is adequate and whether or not the attempts are sufficiently reproducible for diagnosis or to measure control.

How to use a peak flow meter1. Make sure that the mouthpiece is

attached adequately to the body of the meter and that the cursor is on zero.

2. The patient should be standing up straight. However elderly patients or patients who suffer from incontinence may be seated for the test.

3. Inhale deeply, being sure to completely fill the lungs.

4. Place the mouthpiece into the mouth, between the teeth (this is important as the blow must come from the lungs and must not be influenced by the cheeks as is done when the lips are pursed) and close lips securely around it. Make sure the peak flow meter is parallel to the floor.

5. Blow out as hard as possible using as much force as possible. Patients are encouraged not to bend forward while blowing.

6. It is important that there is as little delay as possible between filling the lungs and blowing out.

7. Avoid coughing into the device8. Repeat the test three times returning the

cursor to zero between each blow.9. Use the best of the three blows as your

reading. How to measure and record peak flow ratesPeak flow is determined by height in children and by sex, age and height in adults. The age that children move from the children’s predicted chart to the adult’s one varies according to which company made the chart. However, the values are pretty much the same.

Once a patient’s height has been established and their predicted value has been determined by using a predicted peak flow chart, (See fig 2) the patient can blow into the peak flow meter. Three tests are performed, and presuming there is reproducibility, the best

Fig. 1 Low range and high range peak flow meter


of the three blows is recorded. If this result is less than what is predicted for that patient, it is an indication that obstruction is present. If the patient has reached their predicted result or exceeded it, this is an indication that obstruction of the larger airways is not present.

It is important to remember that these predicted values are only a guide and that while the majority of patients will fall within these parameters, some patients may be below or above them. In these cases, the patient’s best previous peak flow rate becomes his or her predicted rate and so control is determined using their personal best as their predicted.

How do you establish a patients personal best? PEFR varies according to a circadian rhythm; it is lowest in the morning and highest in the afternoon/evening. You need to measure PEFR for a week or two, preferably in the morning before taking any medication (or at least the same time each day). The

highest value or reading taken during that time becomes their personal best.

It is also important to remember that the peak flow done in the clinic is only a reflection of the lung function at that moment and that other considerations including history must be taken into account when determining a diagnosis or control.

Using a peak flow meter in a clinical situation

Reversibility testingReversibility testing can be used either to diagnose asthma or to assess its control.

Once the best of three peak flow readings has been determined and recorded and presuming the peak flow is below what is expected for that patient, you can reverse the patient using a short-acting B2-agonist. Two puffs of salbuta-mol are given, preferably through a spacer. After 15 minutes the peak flow test is repeat-ed, using the best of three blows. If the airway

obstruction has reversed or improved by more than 15%, with a positive history suggestive of asthma, a diagnosis of asthma is confirmed.

How to calculate peak flow reversibilityIf a patient’s baseline peak expiratory flows rate (PEFR) is 120 l/min and the post bronchodilator PEFR is 150 l/min (post bronchodilator reading, subtract pre-bronchodilator reading, divide by pre- bronchodilator reading and multiply by 100).

e.g. 150 – 120 = 30 divide by 120 = 0.25 x 100 = 25%

Patient reversed by 25%

Home monitoring with a peak flow meterIf the patient has a positive history of asthma but the peak flow readings during the consultation are equal or above the patients predicted or personal best, then home monitoring with a peak flow meter may be useful to determine variability.

Once the clinician is happy with the technique, the patient is sent home with both a peak flow meter and a peak flow monitoring chart (See fig 3). They are then instructed to record their peak flow every morning and evening remembering to record the best of three blows each time. Depending on the circumstances they may also be asked to record their peak flow before and after significant events, like exercise or coming into contact with known triggers. They are asked to do this for three to four weeks before returning to the clinician with their records. A variability of 15% or more in the readings is an indication of asthma or poor control.

Exercise induced asthma testingAgain, using the peak flow meter correctly, the best of three blows is ascertained and recorded. The patient is then instructed to run for 6 to 8 minutes on a treadmill, or up and down a passage or stairs, or outside depending on the circumstances and location of the clinic. The peak flow test is then repeated immediately after running and again at 5 and 10 minutes thereafter (adrenaline released during exercise can often mask the EIA until it wears off, hence repeating the peak flow). A drop in peak flow of 15% along with a positive history is an indication of exercise-induced asthma EIA.

Fig. 2. Paediatric predicted peak flow chart


As part of a self management planAll moderate and severe asthmatics should own a peak flow meter as part of their asthma man-agement plan and as a resource in recognizing an exacerbation. By using a peak flow meter along with an action plan they will be better in-formed about when to take their rescue medica-tion and when to start a course of oral steroids. It will also help them to learn what triggers their asthma, and when to seek emergency care.

The general guidelines of an asthma management program using a peak flow meter are set out in Table 1. This is only a guide and the clinician may suggest zones with a smaller range depending on the patients past history of exacerbations.

Conclusion The peak flow meter is a valuable tool for Paedi-atricians and General Practitioners to diagnose and monitor asthma control. It is important that the patient’s technique is correct and that they are able to reproduce their attempts adequately. Clinicians should interpret the readings on the meter in conjunction with the history. It is worth remembering that the peak flow meter only

measures obstruction of the larger airways and that all asthmatics should perform a full lung function, or spirometry at least once a year to assess function of the smaller airways. The peak flow meter is a valuable tool and all clinicians should familiarise themselves with how to use it and interpret the readings.

References• Asthma – Peak flow Meter

http://www.patient.co.uk/health/ Asthma-Peak-Flow-Meter.htm

• Lung function Tests and Asthma By Dr. Shaunagh Emanuel and Dr. Di Hawarden Current

Allergy & Immunology March 2011 Vol 24. No1• Guidelines for the management of chronic

asthma in children – 2009 update. C Motala, RJ Green, AI Manjra, PC Potter, HJ Zar, for the South African Childhood Asthma Working Group (SACAWG)

• www.bing.com/search?q=guide%20lines%20for%20the%20treatment%20of%20chronic%20asthma%20in%2C27495E96F&form=CONMHP &conlogo=CT3210127

• UpToDate Patient information: Asthma treatment in children (Beyond the Basics) www.uptodate.com/contents/asthma-treatment-in-children-beyond-the-basics

Fig. 3. Peak flow monitoring chart

Table 1 - Asthma management program using a peak flow meter (General guidelines)

Green Zone Yellow Zone Red Zone80 to 100 percent of predicted or personal best peak flow rate means all is well. A reading in this zone signifies that the asthma is under control. Continue prescribed controller medications and review other parameters as to the need to reduce medication.

50 to 80 percent of predicted or personal best peak flow rate signals caution. This is an indication that action needs to be taken. Rescue medication is required.

Less than 50 percent of pre-dicted or personal best peak flow rate signals significant obstruction. Immediate action needs to be taken.


Box 1. Asthma control assessment in a pediatric population: comparison between GINA/NAEPP guidelines, Childhood Asthma Control Test (C-ACT), and physician’s rating.4

Authors’ summary: Single measures of asthma control are not able to assess control across the spectrum of asthmatics.

Practical evidence-based advice to assess the control of asthma in childrenProfessor Robin J Green, Dr Adéle PentzDepartment of Paediatrics and Child Health, University of Pretoria

Background: Guidelines recommend regular assessment of asthma control. The Childhood Asthma Control Test (C-ACT) is a clinically validated tool.

Objectives: To evaluate asthma control according to GINA 2006, NAEPP, pediatrician’s assessment (PA), and C-ACT in asthmatic children visiting their ambulatory pediatrician or tertiary care pediatric pulmonologist.

Methods: Demographic data, treatment, and number of severe exacerbations during the previous year were collected. Control was assessed using: (i) strict GINA 2006 criteria, (ii) GINA without taking into account the exacerbation item, (iii) NAEPP criteria, and (iv) PA. Children and parents filled out the C-ACT.

Results: Five hundred and twenty-five children completed the survey (mean age:7.7years;28%≤6years).78%hadacontrollertreatment.58%reported≥1severeexacerbation.C-ACTwas≤19in29.5%.Controlwas not achieved in 76.5%, 55%, 40%, and 34% according to GINA 2006 guidelines, NAEPP guidelines, GINA 2006 without exacerbation criteria,andPA,respectively.C-ACTwassignificantlylowerinchildren≤6 years old (P = 0.002) or with severe exacerbations (P < 0.0001). According to PA, 89% of patients with a C-ACT > 21 were controlled and 85% of patients with a C-ACT < 17 not controlled.

Conclusion: We observed discrepancies between the different tools applied to assess asthma control in children, and the impact of age and exacerbations. Cut-off point of 19 of C-ACT was not associated with the best performance compared to PA. Assessment of control should take into account symptoms and lung function as suggested by the latest GINA guidelines as well as exacerbation over a long period.

uring the last few years some exciting things have happened in the asthma world. The Global Initiative for Asthma published new Guidelines simplifying asthma management.1

We do believe there have been four very important publications guiding the assessment of asthma control in children. These will be summarised in this article.

We know that asthma mortality is falling,2 yet, despite this, there is still a problem with asthma, morbidity. Everybody should by now know the results of the South African study on asthma-related morbidity in a group of South African asthmatics receiving treatment.3

In this project the control status of asthmatic patients in South Africa was ascertained. 3354 individuals indicated that they had asthma. Only 710 respondents met the criteria for analysis, ie. had asthma, presently on medication.

Already 80% of patients who perceive that they have asthma are not receiving anti-inflammatory therapy. And then only 6-8% of the asthmatics on anti-inflammatory therapy were well controlled by way of symptoms. The rest had frequent symptoms.

Lets review the abstracts of the 3 very important papers in recent times that should guide our assessments of asthma control.


Box 3. Disagreement among common measures of asthma control in children.6

Authors’ summary: Asthma is a syndrome of conditions such that a number of assessment tools must be used in conjunction to assess asthma control in children.

Box 2. Overall asthma control: The relationship between current control and future risk.5

Authors’ summary: It is not sufficient to assess asthma control only. Future risk is an important measure.

Background: Asthma guidelines emphasize both maintaining current control and re-ducing future risk, but the relationship between these 2 targets is not well understood.

Objectives:This retrospective analysis of 5 budesonide/formoterol maintenance and reliever therapy (Symbicort SMART Turbuhaler*) studies assessed the relationship between asthma control questionnaire (ACQ-5) and Global Initiative for Asthma-defined clinical asthma control and future risk of instability and exacerbations.

Methods: The percentage of patients with Global Initiative for Asthma–defined controlled asthma over time was assessed for budesonide/formoterol maintenance and reliever therapy versus the 3 maintenance therapies; higher dose inhaled corticosteroid (ICS), same dose ICS/long-acting b2-agonist (LABA), and higher dose ICS/LABA plus short-acting b2-agonist. The relationship between baseline ACQ-5 and exacerbations was investigated. A Markov analysis examined the transitional probability of change in control status throughout the studies.

Background: Asthma is a worldwide problem. It cannot be prevented or cured, but it is possible, at least in principle, to control asthma with modern man-agement. Control usually is assessed by history of symptoms, physical examination, and measurement of lung function. A practical problem is that these measures of control may not be in agreement. The aim of this study was to describe agreement among different measures of asthma control in children.

Methods: A prospective sequential sample of children aged 4 to 11 years with atopic asthma attending a routine follow-up evaluation were studied. Patients were assessed with the following four steps:

1. fraction of exhaled nitric oxide (FENO), 2. spirometry, 3. Childhood Asthma Control Test (cACT), and 4. conventional clinical assessment by a pediatrician. The outcome for

each test was coded as controlled or uncontrolled asthma. Agreement among measures was examined by cross-tabulation and k statistics.

Results: 1. Eighty children were enrolled, and nine were excluded. Mean

FENO in pediatrician judged uncontrolled asthma was double that of controlled asthma (37 vs 15 parts per billion, P=.005).

1. There was disagreement among measures of control. Spirometric indices revealed some correlation, but of the unrelated comparisons, those that agreed with each other most often (69%) were clinical assessment by the pediatrician and the cACT. Worst agreement was noted for FENO and cACT (49.3%).

Conclusion: Overall, different measures to assess control of asthma showed a lack of agreement for all comparisons in this study.

Results: The percentage of patients achieving asthma control increased with time, irrespective of treatment; the percentage Controlled/Partly Controlled at study end was at least similar to budesonide/formoterol maintenance and reliever therapy versus the 3 maintenance therapies: higher dose ICS (56% vs 45%), same dose ICS/LABA (56% vs 53%), and higher dose ICS/ LABA (54% vs 54%). Baseline ACQ-5 score correlated positively with exacerbation rates. A Controlled or Partly Controlled week predicted at least Partly Controlled asthma the following week (80% probability). The better the control, the lower the risk of an Uncontrolled week. The probability of an exacerbation was related to current state and was lower with budesonide/formoterol maintenance and reliever therapy

Conclusion: Current control predicts future risk of instability and exacerbations. Budesonide/formoterol maintenance and reliever therapy reduces exacerbations versus comparators and achieves at least similar control.

Therefore it is now reassuring that GINA have new criteria for assessing asthma in childhood. These are reflected in Table 1.


Table 1. GINA assessment tools for children with asthma1

Asthma symptom control

Day symptomsHow often does the child have cough, wheeze, dyspnea or heavy breathing (number of times per week or day)? What triggers the symptoms? How are they handled?

Night symptomsCough, awakenings, tiredness during the day? (If the only symptom is cough, consider rhinitis or gastroesophageal reflux disease).

Reliever useHow often is reliever medication used? (check date on inhaler or last prescription) Distinguish between pre-exercise use (sports) and use for relieve of symptoms.

Level of activityWhat sports/hobbies/interests does the child have, at school and in their spare time? How does the child’s level of activity compare with their peers or siblings? Try to get an accurate picture of the child’s day from the child without interruption from the parent/carer.

Future risk factors

ExacerbationsHow do viral infections affect the child’s asthma? Do symptoms interfere with school or sports? How long do the symptoms last? How many episodes have occurred since their last medical review? Any urgent doctor/emergency department visits? Is there a written action plan?

Lung functionCheck curves and technique. Main focus is on FEV1 and FEV1 /FVC ratio. Plot these values as percent predicted to see trends over time.

Side-effects Check the child’s height at least yearly. Ask about frequency and dose of ICS and OCS.

Treatment factorsInhaler technique As the child to show how they use their inhaler. Compare with a device-specific checklist.

AdherenceOn how many days does the child use their controller in a week (e.g. 0, 2, 4, 7 days). Is it easier to remember to use it in the morning or evening? Where is inhaler kept – is it in plain view to reduce forgetting? Check date on inhaler.

GoalsDoes the child or their parent/carer have any concerns about their asthma (e.g. fear of medication, side-effects, interference with activity)? What are the child’s/parent’s/carer’s goals for asthma treatment?

Comorbidities

Allergic rhinitisItching, sneezing, nasal obstruction? Can the child breathe through their nose? What medications are being taken for nasal symptoms?

Eczema Sleep disturbance, topical corticosteroids?

Food allergy Is the child allergic to any foods? (confirmed food allergy is a risk for asthma related death).

Other investigations (if needed)

2-week diaryIf no clear assessment can be made based on the above questions, as the child or parent/carer to keep a daily diary of asthma symptoms, reliever use and peak expiratory flow (best of three) for 2 weeks.

Exercise challenge in respiratory laboratory

Provides information about airway hyper responsiveness and fitness. 0nly undertake a challenge if it otherwise difficult to assess asthma control.

FEV1: forced expiratory volume in 1 second; FVC: forced vital capacity; ICS: inhaled corticosteroids; OCS: oral corticosteroids

References1. Global Strategy for Asthma Management and Prevention, Global

Initiative for Asthma (GINA) 2014. Available from: http://www.ginasthma.org/.

2. Zar HJ, Stickells D, Toerien A, Wilson D, Klein M, Bateman ED. Changes in fatal and near fatal asthma in an urban area of South Africa from 1980-1997. Eur Respir J 2001;18:33-37.

3. Green RJ, Davis G, Price D. Perceptions, impact and management of asthma in South Africa: a patient questionnaire study. Prim Care Respir J 2008;17:212-216.

4. Deschildre A, Pin I, El Abu K, et al. Asthma control assessment in a pediatric population: comparison between GINA/NAEPP guidelines, Childhood Asthma Control Test (C-ACT), and physician’s rating. Allergy 2014;69:784–790.

5. Bateman ED, Reddel HK, Eriksson G, et al. Overall asthma control: The relationship between current control and future risk. J Allergy Clin Immunol 2010;125:600-8.

6. Green RJ, Klein M, Becker P, Halkas A, Lewis H, Kitchin O, Moodley T, Masekela R. Disagreement among common measures of asthma control in children. CHEST 2013;143:117-122.


Asthma and pneumococcal disease

Dr Adéle Pentz MBChB(Pret), DCH(SA), FC Paeds(SA), MMed Paeds(Pret), Dip Allerg(SA), Cert Pulm(SA)(Paed), FCCPPaediatric PulmonologistDepartment of Paediatrics, University of Pretoria

treptococcus pneumoniae is the most common respiratory pathogen and a leading cause of community acquired bacterial pneumonia, bacterial meningitis,

sepsis and otitis media and causes significant morbidity and mortality especially at the extremes of age.1 This organism produces a range of virulence factors including the polysaccharide capsule, surface proteins and enzymes, and the toxin pneumolysin.2

Asthma is a chronic reversible obstructive airways disease triggered by multiple factors including viral infections, allergens, irritants or pollution, extreme emotion and exercise.3

For many years doctors have been taught that asthma has nothing to do with bacterial infections, neither in aetiology, nor triggering of symptoms nor exacerbations. What role then, if any, does the pneumococcus play in the setting of asthma?

The pneumococcus and acute asthmaThe current recommendation within guidelines for the management of acute asthma in children and adults is to discourage the routine use of antibiotics for acute exacerbations of asthma. Antibiotic use is restricted to scenarios where there is definite evidence of infection such as fever, purulent sputum, and clinical and/or radiological signs of pneumonia.5

Viruses, most frequently rhinovirus infection, are the most important triggers of asthma exacerbations. Reasons for this phenomenon include the replication of viruses in epithelial cells of the lower airways, cytotoxic effects to the epithelium and a reduced immune response to rhinovirus by atopic asthmatic individuals.6 The newly recognised human rhinovirus C accounts for the majority of asthma exacerbations presenting to hospital, in paediatric patients. Rhinovirus C is also associated with more severe

attacks than human rhinovirus A and B. This is possibly due to different and less efficacious immune responses to human rhinovirus C.7

There is increasing evidence that infection with atypical pathogens may play an important role in the induction of asthma symptoms in the context of chronic persistent asthma or asthma exacerbations. Macrolides have been shown to decrease bacterial adherence and virulence, biofilm formation and mucous hypersecretion.8 Macrolides are however, limited in their efficacy to treat pneumococci because of widespread resistance to macrolides in many parts of the world, including South Africa.

Synergistic relationships between micro-organismsMany studies have suggested the concept of microorganisms acting in synergy during the course of respiratory illness in humans. Viral pathogens and bacterial pathogens, including pneumococcal co-infection, have been documented in individuals with pneumonia.9 The precise interaction of viruses and bacteria, including documentation of the primary offender and mechanistic processes, is still unclear. It is certainly possible that the viruses that trigger asthma exacerbations may, in turn, be ‘turned on’ by bacteria such as pneumococci. Furthermore asthma has been described as an independent risk factor for invasive pneumococcal diasease.10

Therefore, it seems logical, especially in South Africa, where the vaccine is licensed for children and adults, that individuals with asthma be protected against pneumococcal infection through immunisation with the pneumococcal conjugate vaccine. There is evidence that the pneumococcal vaccine decreases the incidence of acute asthma exacerbations, but the evidence is still weak.11

Bacterial aetiology of recurrent wheeze and asthmaThe aetiology of asthma is a much contended debate. Atopy has been shown to be a significant aetiological factor in many parts of the world, but other factors may be at least as important. These include environmental air pollution, passive cigarette smoke exposure, obesity, sedentary lifestyle and a host of other factors.12 Until the findings from the The Copenhagen Prospective Study on Asthma in Childhood (COPSAC) Study were presented it seemed heresy to talk about bacteria in the context of recurrent wheeze and asthma.

The first episode of wheeze in an infant would often be labeled as viral bronchiolitis and there is no good evidence that bacteria play any role in this condition and antibiotic use is not a therapeutic strategy.13,14

Recurrent wheeze in early life, on the other hand, has a number of phenotypic classifications. Probably the most useful of these is the one suggested from Europe classifying episodes as recurrent viral induced wheeze and multi-trigger wheeze, which is most like to become asthma as the child enters school. A number of studies have attempted to define the microbiota associated with recurrent wheeze. Whilst most respiratory viruses are associated with acute bronchiolitis12 it seems that human Rhinovirus (HRV) is particularly associated with recurrent viral induced wheeze (Table 1).15

The role of bacteria in the process of recurrent wheeze and asthma has been controversial. There have been a number of studies documenting the presence of healthy ‘probiotic’ bacteria in the neonatal and infant gut contributing to a lowered incidence of asthma in later life. The mechanism proposed is the influence on T helper cell TH1:TH2 ratio of the immune system to reduce the presence of atopy as the aetiological mechanism for


The concept of exposure to asthmatogenic bacteria that induce a harmful TH1 response, which must be counterbalanced by TH2 immunity, is the theoretical concept introduced by Hans Bisgaard et al to explain the model. The possibility of an innate immune defect that sets up, independently, bacterial colonisation and an asthma phenotype is a possibility. Caution in interpreting this data against the routine use of antibiotics for asthma exacerbations should be noted.

ConclusionMany doctors have the belief that there was little association between pathogenic bacteria, such as the pneumococcus, and wheeze or asthma in children. There is now mounting evidence to suggest that asthma as an outcome of recurrent wheeze may have a close association with early life colonisation

asthma. A recent study by Abrahamsson et al described the association of low gut microbiota diversity in early infancy and the development of asthma by 7 years of age.16

Fewer ‘normal flora’ in the infant gastro-intestinal tract was positively associated with later asthma, suggesting that normal flora help protect against asthma, probably by immunological phenotype changes.

As far back as 2007 Bisgaard and colleagues reported on an association between early life hypo-pharyngeal colonisation by bacteria and subsequent episodes of recurrent and severe wheeze (Table 2).17 The observations were present for Strep. pneumoniae, but strongest for Haemophilus influenzae. In that publication he observed an odds ratio for subsequent asthma development of 4.57 when infants were colonised in early life by bacteria.

by Strep. pneumoniae and H. influenzae. The pneumococcus may, in addition, be important as a co-infecting pathogen, allowing the viruses we know that trigger asthma exacerbations, to be ‘turned on’. It appears that a sub-population of individuals requiring pneumococcal vaccines should include asthmatics. What is not clear yet is the role of antibiotics in the management of recurrent wheeze and asthma and it still seems prudent to recommend that the routine use of antibiotics in acute bronchiolitis, recurrent wheeze and asthma (both acute and chronic) be avoided.

References1. Zhao H, Kang C, Rouse MS, Patel R, Kita H,

Juhn YJ. The role of IL-17 in the association between pneumococcal pneumonia and allergic sensitization. Into J Microbial 2011; 2011:709509. Epub 2011 Nov 17.

2. Mitchell AM, Mitchell TJ. Streptococcus pneumonia: virulence factors and variation. Clin Microbiol Infect 2010; 16:411-418.

3. Motala C, Green RJ, Manjra AI, Potter PC, Zar HJ. Guideline for the management of chronic asthma in children – 2009 update. S Afr Med J 2009; 99:898-912.

4. Kling S, Zar HJ, Green RJ, et al. Guideline for the management of acute asthma in children: 2013 update. S Afr Med J 2013; 103:199-207.

5. Lalloo UG, Ainsley GM, Abdool-Gaffar MS, et al. Guideline for the management of acute asthma in adults: 2013 update. S Afr Med J 2013; 103:188-198.

6. Abbott S. Viral exacerbations of acute lung disease in children. Curr Allergy Clin Immunol 2013; 26(2):59-62.

7. Iwaski J, Smith W, Khoo S, et al. Comparison of rhinovirus antibody titers in children with asthma exacerbations and species-specific rhinovirus infection. Allergy Clin Immunol 2014; 134:25-32.

8. Xepapadaki P, Koutsoumpari I, Papevagelou V, Karagianni C, Papdopoulos G. Atypical bacteria and macrolides in asthma. Allergy Asthma Clin Immunol 2008; 4(3):111-116.

9. Dagan R, Madhi SA, Moore DP. Respiratory viral and pneumococcal coinfection of the respiratory tract: implications of pneumococcal vaccination. Expert Rev Resp Med 2012; 6(4):451.

Table 1. Viral associations with recurrent wheezing in young children17

Viruses% Without recurrent wheezing

% With recurrent wheezing

OR P value

Subjects (n) 124 138

RSV 45.6 31.9 0.9 0.1

RV 3.2 10.9 3.3 <0.05

PIV3 0.8 1.4

hMPV 0.8 0.7Abbreviations: RSV – Respiratory Syncytial Virus; RV – Rhinovirus; PIV3 – Parainfluenza virus type 3; hMPV – human Metapneumovirus

Table 2. Wheeze outcomes in the COPSAC Study for bacterial hypo-pharyngeal colonisation17

End point and bacterial species

Hazard Ratio Adjusted HR

First wheezy episode

Strep pneumonia 1.54 1.53 (0.97 – 2.40)

H influenza 1.49 1.27 (0.82 – 1.97)

Persistent wheeze

Strep pneumonia 1.71 1.41 (0.65 – 3.07)

H influenza 2.85 2.73 (1.36 – 5.48)

Acute severe exacerbations of wheeze

Strep pneumonia 1.80 2.02 (0.79 – 5.17)

H influenza 3.23 3.78 (1.36 – 5.48)

Hospitalization for wheeze

Strep pneumonia 1.90 2.33 (0.72 – 7.54)

H influenza 3.81 4.09 (1.65 – 10.15)Abbreviations: Strep pneumoniae – Streptococcus pneumoniae; H influenzae – Haemophilus influenzae

References 10-17 available on request.


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