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      Preterm birth and childhood wheezing disorders: a systematic review and meta-analysis.

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          Abstract

          Accumulating evidence implicates early life factors in the aetiology of non-communicable diseases, including asthma/wheezing disorders. We undertook a systematic review investigating risks of asthma/wheezing disorders in children born preterm, including the increasing numbers who, as a result of advances in neonatal care, now survive very preterm birth.

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          Innate and adaptive immune responses in asthma.

          Stephen T. Holgate (2012)
          The recognition that asthma is primarily an inflammatory disorder of the airways associated with T helper type 2 (T(H)2) cell-dependent promotion of IgE production and recruitment of mast cells and eosinophils has provided the rationale for disease control using inhaled corticosteroids and other anti-inflammatory drugs. As more has been discovered about the cytokine, chemokine and inflammatory pathways that are associated with T(H)2-driven adaptive immunity, attempts have been made to selectively inhibit these in the hope of discovering new therapeutics as predicted from animal models of allergic inflammation. The limited success of this approach, together with the recognition that asthma is more than allergic inflammation, has drawn attention to the innate immune response in this disease. Recent advances in our understanding of the sentinel role played by innate immunity provides new targets for disease prevention and treatment. These include pathways of innate stimulation by environmental or endogenous pathogen-associated molecular patterns (PAMPs) and danger-associated molecular patterns (DAMPs) to influence the activation and trafficking of DCs, innate sources of cytokines, and the identification of new T cell subsets and lymphoid cells.
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            Role of viral respiratory infections in asthma and asthma exacerbations

            William Busse, Robert Lemanske, James Gern (2010)
            Summary Viral respiratory tract infections are common and usually selflimited illnesses. For patients at risk of asthma, or with existing asthma, viral respiratory tract infections can have a profound effect on the expression of disease or loss of control. New evidence has shown that wheezing episodes early in life due to human rhinoviruses are a major risk factor for the later diagnosis of asthma at age 6 years. For those with existing asthma, exacerbations are a major cause of morbidity, can need acute care, and can, albeit rarely, result in death. Viral respiratory tract infections, predominantly those caused by human rhinoviruses, are associated with asthma exacerbations. There is also evidence that deficiencies in antiviral activity and the integrity of the airway epithelial barrier could make individuals with asthma more likely to have severe viral respiratory infections of the lower airway, and thus increase the risk of exacerbation. In view of the effect of respiratory viruses on many aspects of asthma, efforts to understand the mechanisms and risk factors by which these airway infections cause changes in airway pathophysiology are a first step towards improved treatment.
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              Respiratory syncytial virus and recurrent wheeze in healthy preterm infants.

              Maarten Blanken, Maroeska Rovers, Jorine M Molenaar … (2013)
              Respiratory syncytial virus (RSV) infection is associated with subsequent recurrent wheeze. Observational studies cannot determine whether RSV infection is the cause of recurrent wheeze or the first indication of preexistent pulmonary vulnerability in preterm infants. The monoclonal antibody palivizumab has shown efficacy in preventing severe RSV infection in high-risk infants. In the double-blind, placebo-controlled MAKI trial, we randomly assigned 429 otherwise healthy preterm infants born at a gestational age of 33 to 35 weeks to receive either monthly palivizumab injections (214 infants) or placebo (215 infants) during the RSV season. The prespecified primary outcome was the total number of parent-reported wheezing days in the first year of life. Nasopharyngeal swabs were taken during respiratory episodes for viral analysis. Palivizumab treatment resulted in a relative reduction of 61% (95% confidence interval, 56 to 65) in the total number of wheezing days during the first year of life (930 of 53,075 days in the RSV-prevention group [1.8%] vs. 2309 of 51,726 days [4.5%] in the placebo group). During this time, the proportion of infants with recurrent wheeze was 10 percentage points lower in patients treated with palivizumab (11% vs. 21%, P=0.01). In otherwise healthy preterm infants, palivizumab treatment resulted in a significant reduction in wheezing days during the first year of life, even after the end of treatment. These findings implicate RSV infection as an important mechanism of recurrent wheeze during the first year of life in such infants. (Funded by Abbott Laboratories and by the Netherlands Organization for Health Research and Development; MAKI Controlled Clinical Trials number, ISRCTN73641710.).
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                Author and article information

                Journal
                Journal ID (iso-abbrev): PLoS Med.
                Title: PLoS medicine
                Publisher: Public Library of Science (PLoS)
                ISSN (Electronic): 1549-1676
                ISSN (Print): 1549-1277
                Publication date (Electronic): Jan 2014
                Volume: 11
                Issue: 1
                Affiliations
                [1 ] Department of Paediatrics, Maastricht University Medical Centre, Maastricht, Netherlands ; School for Public Health and Primary Care (CAPHRI), Maastricht University, Maastricht, Netherlands ; Allergy and Respiratory Research Group, Centre for Population Health Sciences, The University of Edinburgh, Edinburgh, United Kingdom.
                [2 ] Department of Paediatrics, Maastricht University Medical Centre, Maastricht, Netherlands.
                [3 ] School for Public Health and Primary Care (CAPHRI), Maastricht University, Maastricht, Netherlands ; Allergy and Respiratory Research Group, Centre for Population Health Sciences, The University of Edinburgh, Edinburgh, United Kingdom.
                [4 ] Department of Paediatrics, Maastricht University Medical Centre, Maastricht, Netherlands ; School for Oncology and Developmental Biology (GROW), Maastricht University Medical Centre, Maastricht, Netherlands ; School of Mental Health and Neuroscience (MHeNS), Maastricht University Medical Centre, Maastricht, Netherlands.
                [5 ] School for Public Health and Primary Care (CAPHRI), Maastricht University, Maastricht, Netherlands.
                [6 ] School for Public Health and Primary Care (CAPHRI), Maastricht University, Maastricht, Netherlands ; Allergy and Respiratory Research Group, Centre for Population Health Sciences, The University of Edinburgh, Edinburgh, United Kingdom ; Harkness Fellow in Health Care Policy and Practice, Division of General Internal Medicine and Primary Care, Brigham and Women's Hospital/Harvard Medical School, Boston, Massachusetts, United States of America.
                Article
                Publisher Item ID: PMEDICINE-D-13-02386
                DOI: 10.1371/journal.pmed.1001596
                PMC ID: 3904844
                PubMed ID: 24492409
                SO-VID: 3cc4b99d-00bd-4d35-92a7-6efad61b1aeb
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