Asthma Abstracts 1



Fish Oil-Derived Fatty Acids in Pregnancy and Wheeze and Asthma in Offspring.
            (Bisgaard et al., 2016) Download
Background Reduced intake of n-3 long-chain polyunsaturated fatty acids (LCPUFAs) may be a contributing factor to the increasing prevalence of wheezing disorders. We assessed the effect of supplementation with n-3 LCPUFAs in pregnant women on the risk of persistent wheeze and asthma in their offspring. Methods We randomly assigned 736 pregnant women at 24 weeks of gestation to receive 2.4 g of n-3 LCPUFA (fish oil) or placebo (olive oil) per day. Their children formed the Copenhagen Prospective Studies on Asthma in Childhood2010 (COPSAC2010) cohort and were followed prospectively with extensive clinical phenotyping. Neither the investigators nor the participants were aware of group assignments during follow-up for the first 3 years of the children's lives, after which there was a 2-year follow-up period during which only the investigators were unaware of group assignments. The primary end point was persistent wheeze or asthma, and the secondary end points included lower respiratory tract infections, asthma exacerbations, eczema, and allergic sensitization. Results A total of 695 children were included in the trial, and 95.5% completed the 3-year, double-blind follow-up period. The risk of persistent wheeze or asthma in the treatment group was 16.9%, versus 23.7% in the control group (hazard ratio, 0.69; 95% confidence interval [CI], 0.49 to 0.97; P=0.035), corresponding to a relative reduction of 30.7%. Prespecified subgroup analyses suggested that the effect was strongest in the children of women whose blood levels of eicosapentaenoic acid and docosahexaenoic acid were in the lowest third of the trial population at randomization: 17.5% versus 34.1% (hazard ratio, 0.46; 95% CI, 0.25 to 0.83; P=0.011). Analyses of secondary end points showed that supplementation with n-3 LCPUFA was associated with a reduced risk of infections of the lower respiratory tract (31.7% vs. 39.1%; hazard ratio, 0.75; 95% CI, 0.58 to 0.98; P=0.033), but there was no statistically significant association between supplementation and asthma exacerbations, eczema, or allergic sensitization. Conclusions Supplementation with n-3 LCPUFA in the third trimester of pregnancy reduced the absolute risk of persistent wheeze or asthma and infections of the lower respiratory tract in offspring by approximately 7 percentage points, or one third. (Funded by the Lundbeck Foundation and others; number, NCT00798226 .).

Asthma: eosinophil disease, mast cell disease, or both?
            (Bradding, 2008)  Download
Although there is much circumstantial evidence implicating eosinophils as major orchestrators in the pathophysiology of asthma, recent studies have cast doubt on their importance. Not only does anti-interleukin-5 treatment not alter the course of the disease, but some patients with asthma do not have eosinophils in their airways, whereas patients with eosinophilic bronchitis exhibit a florid tissue eosinophilia but do not have asthma. In contrast, mast cells are found in all airways and localize specifically to key tissue structures such as the submucosal glands and airway smooth muscle within asthmatic bronchi, irrespective of disease severity or phenotype. Here they are activated and interact exclusively with these structural cells via adhesive pathways and through the release of soluble mediators acting across the distance of only a few microns. The location of mast cells within the airway smooth muscle bundles seems particularly important for the development and propagation of asthma, perhaps occurring in response to, and then serving to aggravate, an underlying abnormality in asthmatic airway smooth muscle function. Targeting this mast cell-airway smooth muscle interaction in asthma offers exciting prospects for the treatment of this common disease.

The Hypochlorhydria of Asthma in Childhood
            (Bray, 1931)  Download
From the earliest times ‘digestive upsets’ have been noted by all observers in association with the asthmatic habitude, and dietetics have proved one of the main strongholds of the therapeutists.

Cyanocobalamin in asthma
            (Crocket, 1957)  Download
Occasional refererence has been made to clinical improvement in asthma following the administration of cyanocobalamin (vitamin B 12) for other disease states. The first report appears to have been that of Wetzelet al. (1949).

A real sugar high? Wheeze and associated hyperglycemia
            (Dieppe et al., 2009)  Download
We present the case of a 13-month-old boy who initially presented with a 2-day history of cough and coryzal symptoms with significant wheeze and a respiratory acidosis. His viral-induced wheeze was initially treated with nebulized salbutamol and oral prednisolone, but then, he went on to develop hyperglycemia, ketonuria, and glycosuria with a partially compensated metabolic acidosis. We discuss the differential diagnoses of salbutamol-induced lactic acidosis, steroid-induced hyperglycemia, new presentation of diabetic ketoacidosis, or transient hyperglycemia. We then focus on transient hyperglycemia and the risk of the progression of this clinical entity to insulin-dependent diabetes mellitus.

Effect of vitamin B12 in asthma
            (Kaufman, 1951)  Download
Marked improvement in a patient with asthma was noted by Wetzel during administration of oral vitamin B12 in doses of 10 micrograms daily. Of the eight patients to whom vitamin B12 was administered, there was improvement in only one individual.

Celiac disease confers a 1.6-fold increased risk of asthma: a nationwide population-based cohort study
            (Ludvigsson et al., 2011)  Download
Through the personal identity number, we matched nationwide data on small intestinal biopsies with the Swedish National Patient Register (containing both inpatient care and hospital outpatient care) to examine the risk of asthma in patients with CD.

The etiologies, pathophysiology, and alternative/complementary treatment of asthma
            (Miller, 2001) Download
A chronic inflammatory disorder of the respiratory airways, asthma is characterized by bronchial airway inflammation resulting in increased mucus production and airway hyper-responsiveness. The resultant symptomatology includes episodes of wheezing, coughing, and shortness of breath. Asthma is a multifactorial disease process with genetic, allergic, environmental, infectious, emotional, and nutritional components. The underlying pathophysiology of asthma is airway inflammation. The underlying process driving and maintaining the asthmatic inflammatory process appears to be an abnormal or inadequately regulated CD4+ T-cell immune response. The T-helper 2 (Th2) subset produces cytokines including interleukin-4 (IL-4), IL-5, IL-6, IL-9, IL-10, and IL-13, which stimulate the growth, differentiation, and recruitment of mast cells, basophils, eosinophils, and B-cells, all of which are involved in humoral immunity, inflammation, and the allergic response. In asthma, this arm of the immune response is overactive, while Th1 activity, generally corresponding more to cell-mediated immunity, is dampened. It is not yet known why asthmatics have this out-of-balance immune activity, but genetics, viruses, fungi, heavy metals, nutrition, and pollution all can be contributors. A plant lipid preparation containing sterols and sterolins has been shown to dampen Th2 activity. Antioxidant nutrients, especially vitamins C and E, selenium, and zinc appear to be necessary in asthma treatment. Vitamins B6 and B12 also may be helpful. Omega-3 fatty acids from fish, the flavonoid quercetin, and botanicals Tylophora asthmatica, Boswellia serrata and Petasites hybridus address the inflammatory component. Physical modalities, including yoga, massage, biofeedback, acupuncture, and chiropractic can also be of help.

Breathing Easier with Fish Oil - A New Approach to Preventing Asthma
            (Ramsden, 2016) Download
Although these results are highly promising, a note of caution is warranted. The dose of EPA plus DHA provided in this trial (2.4 g per day) was approximately 15 to 20 times as high as the average U.S. intake from foods. Before these findings can be applied to clinical practice, it is therefore imperative to ensure that this dose had no adverse effects on behavior, cognition, or other long­term outcomes. Future work is also needed to determine whether lower doses are effective and whether these results can be replicated in other populations.

Why do the published data fail to clarify the relationship between gastroesophageal reflux and asthma
            (Sontag, 2000)  Download
The relationship between gastroesophageal reflux (GER) and asthma has troubled physicians for centuries and has been a source of debate among pulmonologists, allergists, and gastroenterologists for decades. Attempting to tie together the pieces of the puzzle, numerous investigators have struggled to show that in patients with asthma, GER symptoms occur too frequently, gastric acid dwells for too long in the esophageal lumen, and refluxed gastric acid injures the esophageal mucosa more than expected. Unfortunately, all of the work done by these fine investigators has failed to demonstrate a "cause and effect" relationship. Although they have succeeded in convincing us that GER occurs more frequently in asthmatics than in nonasthmatics, they still must continue until we all know how to predict which patients have gastroesophageal-induced or gastroesophageal-exacerbated asthma.

Serum B12 tryptase level as a marker of allergic airway inflammation in asthma
            (Taira et al., 2002)  Download
Tryptase is a specific marker of mast-cell activation and plays a part in the pathophysiology of various allergic diseases including asthma, but little is known of the spillover of this enzyme into the systemic circulation. Therefore, we measured serum levels of mast-cell-derived tryptase in 21 patients with mild to moderate asthma and 20 healthy, subjects, using a B12 monoclonal antibody-based immunofluoroassay that detects both monomers and tetramers of alpha- and beta-tryptases. There was a good correlation between serum and sputum tryptase levels, and, compared with healthy subjects (1.68 +/- 0.31 ng/ml), asthma patients had higher concentrations of serum tryptase (atopic asthma, 4.18 +/- 0.95 ng/ml, p = 0.022; nonatopic asthma, 3.93 +/- 0.82 ng/ml, p = 0.031). Although serum tryptase levels did not correlate with asthma symptom scores, peak expiratory flow, or forced expiratory volume in 1 s, they positively correlated with mast-cell and eosinophil counts (p = 0.041 and p = 0.025, respectively) and eosinophil cationic protein contents (p = 0.029) in induced sputum. These results suggest that serum tryptase detected with B12 antibody is a marker of allergic airway inflammation in asthma.



Bisgaard, H, et al. (2016), ‘Fish Oil-Derived Fatty Acids in Pregnancy and Wheeze and Asthma in Offspring.’, N Engl J Med, 375 (26), 2530-39. PubMed: 28029926
Bradding, P (2008), ‘Asthma: eosinophil disease, mast cell disease, or both?’, Allergy Asthma Clin Immunol, 4 (2), 84-90. PubMed: 20525129
Bray, G.W. (1931), ‘The Hypochlorhydria of Asthma in Childhood’, QJM, 24 (94), 181-97. PubMed:
Crocket, J. A. (1957), ‘Cyanocobalamin in asthma’, Acta Allergol, 11 (4), 261-68. PubMed: 13497448
Dieppe, C., S. Verma, and B. Wilson (2009), ‘A real sugar high? Wheeze and associated hyperglycemia’, Am J Emerg Med, 27 (3), 368 e1-e2. PubMed: 19328388
Kaufman, R. E. (1951), ‘Effect of vitamin B12 in asthma’, Ann Allergy, 9 (4), 517-18. PubMed: 14847439
Ludvigsson, J. F., et al. (2011), ‘Celiac disease confers a 1.6-fold increased risk of asthma: a nationwide population-based cohort study’, J Allergy Clin Immunol, 127 (4), 1071-73. PubMed: 21315431
Miller, A. L. (2001), ‘The etiologies, pathophysiology, and alternative/complementary treatment of asthma’, Altern Med Rev, 6 (1), 20-47. PubMed: 11207455
Ramsden, CE (2016), ‘Breathing Easier with Fish Oil - A New Approach to Preventing Asthma’, N Engl J Med, 375 (26), 2596-98. PubMed: 28029914
Sontag, SJ (2000), ‘Why do the published data fail to clarify the relationship between gastroesophageal reflux and asthma’, Am J Med, 108 Suppl 4a 159S-69S. PubMed: 10718471
Taira, M., et al. (2002), ‘Serum B12 tryptase level as a marker of allergic airway inflammation in asthma’, J Asthma, 39 (4), 315-22. PubMed: 12095181