News Beyond Our Pages
Authors: Marc E. Rothenberg, Jean Bousquet
Journal: Journal of Allergy and Clinical Immunology (2018)

A mainstay in the pharmacologic treatment of asthma is stepwise escalation from short-acting β2-agonist monotherapy to additional therapy with long-acting β2-agonists (LABAs) and inhaled glucocorticoids. The importance of long-acting muscarinic antagonists (LAMAs) has been accepted by guidelines, such as the Global Initiative for Asthma. Sobieraj et al have performed 2 systematic reviews and meta-analyses regarding the management of asthma. The first review (JAMA 2018;319:1473-84; https://doi.org/10.1001/jama.2018.2757) focused on the efficacy of LAMAs as an add-on therapy to inhaled glucocorticoids in adolescent and adult patients with uncontrolled asthma. Data were pooled from 15 placebo-controlled, randomized controlled trials of a combined 7122 patients with asthma whose symptoms were uncontrolled by low- or medium-dose inhaled corticosteroids (ICSs) in which addition of LAMAs was compared with addition of either placebo or LABAs. Use of LAMAs was associated with decreased risk of exacerbations requiring systemic corticosteroids compared with placebo, with an absolute risk reduction of 2%. Compared with adding a LABA, adding a LAMA as adjunct therapy to ICSs did not demonstrate statistically significant benefit. Finally, addition of LAMAs to LABAs and ICSs (triple therapy) did not reduce asthma exacerbations compared with addition of LABAs and ICSs alone.These analyses support the efficacy of 2 treatment strategies for the management of persistent asthma in adolescents and adults These analyses support the efficacy of 2 treatment strategies for the management of persistent asthma in adolescents and adults The second review (JAMA 2018;319:1485-96; https://doi.org/10.1001/jama.2018.2769) focused on the efficacy of use of ICSs and LABAs together as quick-relief therapy (single maintenance and reliever therapy). A pooled analysis was performed of 16 separate clinical trials involving 341 children aged 4 to 11 years and 22,524 patients aged 12 years and older with asthma. Single maintenance and reliever therapy was associated with lower risk of asthma exacerbations compared with either same-dose or higher-dose ICSs and LABAs in patients 12 years and older. Evidence in patients 4 to 11 years old was limited. In summary, these articles support the addition of LAMAs to ICSs and the combined use of ICSs and LABAs as controller and quick-relief therapy as strategies to reduce asthma exacerbations. We asked first author Diana Sobieraj, PharmD, BCPS, of the University of Connecticut School of Pharmacy, Storrs, Connecticut, to comment on the study. She writes, “Our analysis found that the combined use of ICSs and LABAs as both controller and quick-relief therapy in patients with persistent asthma who were aged 12 years and older significantly reduced the risk of asthma exacerbations compared with traditional ICSs and LABAs used as controller therapy with a short-acting β2-agonist used as quick relief. In a separate analysis we found adding a LAMA to an ICS reduced the risk of asthma exacerbation in patients 12 years of age and older with uncontrolled persistent asthma. Together, our analyses support the efficacy of 2 treatment strategies for the management of persistent asthma in adolescents and adults.” The use of antibiotics and acid-suppressive medications can induce durable changes in the gut microbiome. Because alterations in the microbiome increase the risk of allergic diseases, Mitre et al performed a retrospective cohort study (JAMA Pediatr 2018; https://doi.org/10.1001/jamapediatrics.2018.0315) using a large electronic military personnel database of 792,130 children to assess whether the use of antibiotics or acid-suppressive medications (histamine 2 receptor antagonist [H2RA] or proton pump inhibitor [PPI]) within the first 6 months of life predisposes to later development of allergic disease. Allergic disease was defined as the presence of food allergy, atopic dermatitis, asthma, anaphylaxis, allergic rhinitis, allergic conjunctivitis, urticaria, contact dermatitis, medication allergy, or other allergy. Of 792,130 children, 7.6% were prescribed an H2RA, 1.7% were prescribed a PPI, and 16.6% were prescribed an antibiotic during the first 6 months of life. Increased risk of every allergic disease category was observed with prescription of H2RAs, PPIs, or antibiotics, with most associations being stronger for use of H2RAs or PPIs compared with antibiotics. The adjusted hazard ratios varied from 1.4 to 2.1, indicating substantial increased risk. Among the different allergic diseases tested, food allergy had the highest association with use of H2RAs or PPIs, whereas asthma had the highest association with antibiotic use. On the basis of these results, as well as those of prior animal and human studies they cite, the authors conclude that the use of acid-suppressive medications or antibiotics might predispose to development of allergic diseases in early childhood. Further studies are required to determine whether the relationship is causal and, if so, whether it is due to alterations in the gut microbiome.The use of acid-suppressive medications or antibiotics might predispose to development of allergic diseases in early childhood The use of acid-suppressive medications or antibiotics might predispose to development of allergic diseases in early childhood We asked first author Edward Mitre, MD, Associate Professor in the Department of Microbiology and Immunology at the Uniformed Services University of the Health Sciences, Bethesda, Maryland, to comment on the study. He writes, “Antacid medications are considered generally harmless and something to try with fussy babies who spit up a lot. Our results, in conjunction with those of other animal and human studies, suggest we should be more cautious prescribing these medicines in infants.” It is increasingly appreciated that childhood factors and accelerated decrease in lung function, as measured by FEV1, predispose to later development of chronic obstructive pulmonary disease (COPD). Bui et al (Lancet Respir Med 2018; https://doi.org/10.1016/S2213-2600[18]30100-0) used data from 2438 subjects in the Tasmanian Longitudinal Health Study to model lung function trajectories based on FEV1 values obtained at the ages of 7, 13, 18, 45, 50, and 53 years. The authors stratified the study participants into 6 distinct trajectories based on how lung function changes with age, including 3 trajectories with increased risk for COPD: early below average with accelerated decrease, persistently low, and below average. These 3 trajectories were linked to 75% of COPD burden, including all cases of moderate-to-severe COPD. Additionally, these 3 trajectories were associated with childhood asthma, bronchitis, pneumonia, allergic rhinitis, eczema, parental asthma, and maternal smoking. Finally, the effect of childhood asthma and maternal smoking on the early below average with accelerated decrease trajectory was enhanced by personal smoking and asthma in adulthood. In total, the authors have identified lung function trajectories beginning in childhood that predispose to later development of COPD and propose action to minimize adverse lung function trajectories, such as by reducing smoking and encouraging immunizations to decrease COPD burden.Lung function trajectories beginning in childhood predispose to later development of COPD Lung function trajectories beginning in childhood predispose to later development of COPD Pulmonary neuroendocrine cells (PNECs) constitute a rare and enigmatic airway epithelial cell population that secretes neuropeptides and neurotransmitters. Sui et al (Science 2018; https://doi.org/10.1126/science.aan8546) identified a novel role for this unique cell type in pulmonary type 2 immune response. PNECs were found close to group 2 innate lymphoid cells at airway branch points in mice. PNECs directly stimulated type 2 cytokine production from group 2 innate lymphoid cells through release of calcitonin gene-related peptide and induction of goblet cell hyperplasia through release of the neurotransmitter gamma-aminobutyric acid. Mice genetically deficient in PNECs (through deficiency of the transcription factor Ascl1) had diminished type 2 immune responses and goblet cell hyperplasia in experimental aeroallergy, and this effect was reversed with exogenous application of a mixture of calcitonin gene-related peptide and gamma-aminobutyric acid. Finally, lungs from human asthmatic patents showed increased presence of PNECs. These collective results demonstrate that PNECs and innate lymphoid cells form a neuroimmunologic module at airway branch point junctions to promote allergy. Image used via Wikimedia Commons, created by user Yale Rosen [CC BY-SA 2.0 (https://creativecommons.org/licenses/by-sa/2.0)], via Wikimedia Commons.PNECs and group 2 innate lymphoid cells form a neuroimmunologic module at airway branch point junctions to promote allergyNews items were written by medical writer Jared Travers, PhD.Find more News Beyond Our Pages online at www.jaci-nbop.blogspot.com. PNECs and group 2 innate lymphoid cells form a neuroimmunologic module at airway branch point junctions to promote allergy News items were written by medical writer Jared Travers, PhD. Find more News Beyond Our Pages online at www.jaci-nbop.blogspot.com.