Asthma


Table 4: Possible Criteria for Steroid Responsiveness in Children with Severe Asthma


Domain Symptoms Lung Function Requirement


Asthma control test rises to ≥20/25, or by at least 5 points


FEV1 rises to normal (≥-1.96 Z-score),or by ≥15 %


No residual bronchodilator response


Inflammatory Markers If paired induced sputum samples available


If paired induced sputum samples not available


Sputum eosinophil count normal (≤2.5 %)


FeNO* normal (<24 ppb)58


FeNO* = exhaled nitric oxide measured at flow 50 ml/s; FEV1 = forced expiratory volume in one second.


Non-response = no improvement in any dimension; partial response = one or two domains improve; complete response = all three domains normalise.


to which parents directly oversee the taking of medication is checked. In a recent series, medication issues contributed in nearly half of the children.44


Many patients with asthma do not fill


furry pets were common culprits, and there was great reluctance to address the problem.44


There is considerable evidence that fungal sensitisation and exposure are associated with increased morbidity and severity of asthma, including really severe exacerbations.61–63


It would seem simpler to


undertake a trial of addressing mould exposure, possibly in combination with oral anti-fungals, before escalating therapy or using toxic steroid sparing agents.


Psychosocial Issues


In many cases, these issues are only identified at the home visit. Psychological risk factors were prominent in children and young adults who subsequently died of asthma,64,65 asthma episodes.66 children,67


or suffered from near-fatal There is evidence that stress worsens asthma in positive effect.68 teosinophilic inflammation and trigger asthma exacerbation.69 Prescription uptake data from primary care are


also routinely collected to calculate the total amount of medication to which the child has access.45


their ICS prescriptions (‘primary’ non-adherence), and such a possibility should be properly investigated in a child with severe uncontrolled asthma.46


The Home and Around Home Environment


Fireplaces, woodstoves, kerosene heaters and gas for cooking have been associated with increased asthma morbidity.47


Installing


non-polluting, more effective heating in the homes of children with asthma may significantly reduce symptoms.48


Factors such as


traffic pollution and external aeroallergen exposure may have important effects on asthma.49


Less obvious factors within the


neighbourhood, such as violence and socioeconomic deprivation may also affect asthma.50


Passive and Active Exposure to Tobacco Smoke Exposure to passive smoking is common in asthmatic children. There is increasing evidence that tobacco smoke exposure may lead to steroid-resistant asthma.51,52


which could be counteracted by life events with a definite Studies have shown that stress can increase Little is


known about the biological mechanisms responsible for these effects. However, psychological distress may influence asthma through neuro-immunological mechanisms70 resistance.71


and the induction of steroid


Psychosocial issues can also manifest as dysfunctional breathing, including hyperventilation and vocal cord dysfunction, which frequently co-exist with asthma.


The Multidisciplinary Planning Meeting


After completion of the collection of all these data, a detailed team discussion is imperative. In more than 50 % of cases, it is clear that there are potentially reversible factors that account for the problem.44 These children are considered as having ‘difficult asthma’. In those children in whom reversible factors have not been identified and basic management is deemed to be good, a further programme of investigations is recommended.


Step Four – Characterisation of Severe, Therapy-resistant Asthma


Every effort should be made


to help parents quit smoking, including referrals to smoking cessation clinics.


Allergen Exposure


Aeroallergen sensitisation is common in children with severe asthma.14,15,17,18


High levels of allergens to which the child is sensitised in the home in combination with viral infection gives a high odds ratio for admission to hospital with an asthma attack;53 furthermore, multiple allergic sensitisations are associated with recurrent acute exacerbations.54,55


Although no study has shown


that reducing the allergen burden in the home will improve asthma control in children with really severe asthma, there is logic for avoiding allergens in this asthma phenotype.56


Allergen exposure in


schools might also be important; however, this possibility is an even more difficult area in which to intervene.57


There is at least


biological plausibility for allergen reduction. Allergens cause steroid insensitivity by an interleukin (IL)-2 and IL-4-dependent mechanism.58,59


for example, proteolysis.60


Many allergens also have non-IgE-mediated effects, Thus the rationale of allergen avoidance


in children with really severe asthma is strong. In a recent series, 94


• Is there concordance between symptoms and airway inflammation? • • •


What is the pattern of cellular inflammation? Is the child steroid responsive?


Does the child have persistent airflow limitation?


In summary, the child is assessed on two occasions, before and after a steroid trial with a single intramuscular injection of triamcinolone, in the domains of symptoms (Asthma Control Test);72


Children whose ‘difficult’ asthma remains uncontrolled despite resolution of any reversible factors are termed ‘severe therapy-resistant’ asthmatics. These children should undergo an individualised treatment plan after a detailed and invasive protocol of investigations, including bronchoscopy and assessment of the response to corticosteroids. Before planning treatment, the aim is to answer four questions using this protocol.


lung function


(spirometry before and after acute administration of short-acting β-2 agonist); and airway inflammation (exhaled nitric oxide, induced sputum) (see Table 4). A fibreoptic bronchoscopy is performed, with bronchoalveolar lavage and endobronchial biopsy. The use of innovative ‘-omics’ technologies, such as proteomics and metabolomics, may offer great potential in the future.73


As with much


in the field, there is no evidence to support this protocol, which has been described in detail elsewhere.3


EUROPEAN RESPIRATORY DISEASE


Page 1  |  Page 2  |  Page 3  |  Page 4  |  Page 5  |  Page 6  |  Page 7  |  Page 8  |  Page 9  |  Page 10  |  Page 11  |  Page 12  |  Page 13  |  Page 14  |  Page 15  |  Page 16  |  Page 17  |  Page 18  |  Page 19  |  Page 20  |  Page 21  |  Page 22  |  Page 23  |  Page 24  |  Page 25  |  Page 26  |  Page 27  |  Page 28  |  Page 29  |  Page 30  |  Page 31  |  Page 32  |  Page 33  |  Page 34  |  Page 35  |  Page 36  |  Page 37  |  Page 38  |  Page 39  |  Page 40  |  Page 41  |  Page 42  |  Page 43  |  Page 44  |  Page 45  |  Page 46  |  Page 47  |  Page 48  |  Page 49  |  Page 50  |  Page 51  |  Page 52  |  Page 53  |  Page 54  |  Page 55  |  Page 56  |  Page 57  |  Page 58  |  Page 59  |  Page 60  |  Page 61  |  Page 62  |  Page 63  |  Page 64  |  Page 65  |  Page 66  |  Page 67  |  Page 68  |  Page 69  |  Page 70  |  Page 71  |  Page 72  |  Page 73  |  Page 74  |  Page 75  |  Page 76