Asthma: Concept, Causes, Consequences
This case is a fairly direct representation of a child with viral-induced wheeze and background history of asthma. Asthma itself is a manifestation of recurrent reversible bronchoconstriction of the conducting airways, usually due to a trigger (immunological reaction) leading to symptoms of breathlessness, chest tightness, wheezes, increased work of breathing, and cough (at night and/or in the early morning)2. It is a leading chronic disease worldwide and according to the World Health Organization, is estimated to become the third leading cause of death by the year 20207. Even though asthma can be caused by various aetiologies, similar pathogenesis occurs after exposure to different allergens where it can aggravate symptoms in those who are genetically susceptible4.In response to environmental exposure and/or viral infection, atopic asthmatics such as A.O mediate TH2 response to secrete cytokines (IL-4, IL-5, IL-13) promoting inflammation and stimulating B cells to produce IgE. Chemokines secreted from T cells and epithelial cells would also recruit more T cells and eosinophils which aggravates the reaction. Concurrently, IgE binds to submucosal mast cells where it releases granule and cytokines inducing an early phase reaction and a late-phase reaction. The early phase reaction promotes bronchoconstriction, increasing of mucus production and vascular permeability and vasodilation. The late phase reaction is the recruitment phase for leukocytes
Genetic predisposition:About half of asthmatic patients have a family history of asthma and/or atopies which evidently supports the reason that a major criteria in the Asthma Predictive index would include a diagnosed asthmatic in one parent5. Within the Asthma Predictive index, the other major criteria is eczema in the child diagnosed by a physician. Minor criteria’s include allergic rhinitis, wheezing apart from colds, and peripheral eosinophilia greater than or equal to 4%. According to the Asthma Predictive index, if a child is less than 3 years old who has had more than or equal to 3 significant wheezy episodes in a year will have a high likelihood of asthma if confirmed with 1 major and 2 minor criteria. Thus, as aforementioned, genetic predisposition in the child is only partially to blame.In order to recognize genetic susceptibility in different asthma phenotypes, methods such as familial aggregation and twin studies, segregation analysis, linkage studies, candidate-gene association studies and functional genomics were conducted. The studies have identified certain gene complexes such as ADAM33, PHF11, DPP10, GRPA, and SPINK5. And in particular, the polymorphisms in the gene encoding the metalloproteinase ADAM33 suggests increased proliferation of bronchial smooth muscle and fibroblasts, leading to possible bronchial hyperreactivity and subepithelial fibrosis2. Multiple chromosomal regions of 5q, 6p, 11q, 12q, and 13q also provide evidence for linkage studies
Notably, a susceptible locus on chromosome 5q is located near the gene cluster encoding the cytokines IL-3, IL-4, IL-5, IL-9, and receptors of IL-3 and IL-4 those which are responsible for regulating IgE and the development and progression of inflammation recognized in the pathophysiology of asthma2. Within the cytokines, the polymorphism in IL-4 and IL-13 gene displays the strongest and most consistent associations with asthma or atopic disease2,6. In the case of A.O, he would have been diagnosed with asthma with the Asthma Predictive index under the association that his father is an asthmatic and he has eczema. However, it is uncertain whether or not he would have been diagnosed due to which of the other two in the minor criteria.
Smoking:Besides respiratory viral infections which are most commonly due to parainfluenza virus, rhinovirus type C, and respiratory syncytial virus (RSV), other common triggers of asthma are environmental factors such as tobacco smoke, pet dander, dust mites, and air pollutants. Within the history, it is important to ask about any other ill family members at home to confirm a possibility of a virus. As well as an open question such as “Are there any smokers at home?”, in which the parents or caretakers would add whether or not the smoker smokes indoors or outdoors. However, studies have proven that there is no benefit in reducing the risk of exposure to second-hand smoke in children even if the smoker exclusively smokes outdoors 10,11. This study led to the recognition of thirdhand smoke, which is a newly recognized health risk, such that the environment is contaminated due to the lingering of tobacco smoke after it has been extinguished. This is then believed that the chemicals left on smokers clothes would be inhaled by children after returning indoors, thus leading to the adverse respiratory effects as damaging as primary exposure or second-hand smoking. Furthermore, a study suggested that a form of ultrafine particles produced from thirdhand smoke reacting with ozone could exacerbate asthma symptoms, as well as, another study showing evidence of DNA damage in genes exposed to thirdhand smoke12. Parental perspective towards smoking and the health risk towards their children has seen to slowly make progress. An approach in epidemiological studies suggests that the urine cotinine measurements are a powerful predictor of the child’s actual exposure to the amount of smoke rather than to parental self-report. Even though Cotinine Creatinine Ratio (CCR) is a marker widely used for tobacco exposure, research showed no association in which most of the parents believe that smoke exposure having no negative effects on asthma in children8,9.
Thus, it is needless to say that even though tobacco smoke in Ireland has been banned nationwide, and neonatal complications nearly showed an immediate decrease, however, thirdhand smoke still exists in the environment. It is lingering on the clothing of those other parents who brings their child to school and lingering in every corner of the house where smokers such as A.O’s father still exist. It can cause acute exacerbations of bronchial hyperreactivity, and although not usually measured as a parameter in children, a decrease in FEV1 and FEV1/FVC. Measures should be taken beginning in utero of the exposure to maternal smoking (provoking poor lung function in infancy and risk of asthma for the first 7 years of life) until postnatal, to decrease any possibility of asthma or recurrent wheezing illnesses10.Diary/Milk and Asthma:What was striking was the mother mentioned that there was a variance in her child’s episodes of asthmatic exacerbations, in which she thought the dairy products (such as the milk her child would take before bed or the cream he had during dinner) were partially contributing to the worsening of symptoms. There is a widespread myth still upheld today among parents of asthmatic children linking milk consumption and asthma. The belief that drinking milk would increase mucus production and/or aggravate asthmatic symptoms still exist.
In a study of 21 subjects (11 asthmatics and 10 without asthma), ingested whole milk and were measured at 30-minutes intervals for 3 hours showed no changes in FEV1 or forced expiratory flow at 50%, but a decreased DLCO in asthmatics over the 3 hours3. Another study conducted over 20 subjects initially started with 2-week dairy-free diet then an active challenge of 300mL of milk. This particular study displayed a 15% reduction in both FEV1 and peak expiratory flow on the active challenge day in 4 subjects, which was compared with a placebo day obtained at the same time3. Both studies mentioned above have no details as to the age of the subject and the baseline status of current asthmatics, thus demonstrating a lack of scientific evidence to support such a theory.
Another particular single-blinded study however introduced 13 children (aged 3-14 years) to receive a milk-free diet under 8 weeks, where 9 children continued with their normal diet. Remarkably, children on the milk-free diet had PEF rate higher than 5 children in the control group3. Another hypothesis suggests that b-casomorphin-7, a protein derived from milk breakdown is known to upregulate MUC5AC gene expression on gut glands to stimulate mucus production. However, only in the condition where there is active inflammation of the intestine giving way for permeability of milk proteins entering the systemic circulation14. In this case where A.O presenting with a viral cold, shows no correlation to an increased intestinal inflammation and permeability, thus this hypothetical theory seems improbable in his situation.Dairy products, especially milk, is not suggested to be eliminated in a child’s regular diet, if not more so in the asthmatic child on preventer corticosteroid medications (risk of brittle bones). Dairy products which are the main source of calcium is essential for a child’s development during growth spurts to aim for maximum bone density and normal growth development.
