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microRNAs in asthma: potential therapeutic targets

imagePurpose of review: Asthma is a global disease affecting millions of people. Current treatments are largely symptomatic and, although often effective, can be associated with various side effects. microRNAs (miRNAs/miRs) are regulatory RNAs that affect protein synthesis. They represent new therapeutic targets, and medicines that target specific miRNAs may have potential in the treatment of asthma. Recent findings: There have been a number of studies in the field of miRNA that implicate specific miRNAs in the pathophysiology of asthma. For example, studies using mouse models have identified miRNAs that are altered in response to allergen challenge. Certain miRNAs that are involved in the regulation of interleukin-13 and the TH2 response, key components of the asthmatic response, have been shown to be amenable to modulation by premiRs and antimiRs. Other studies have identified miRNAs that are implicated in bronchial smooth muscle hyperresponsiveness and proliferation. Single-nucleotide polymorphisms in miRNA responsive elements within asthma susceptibility genes, and also in miRNAs themselves, can also contribute to the asthma phenotype. Summary: Developing miRNA-based medicines to treat the pulmonary manifestations of asthma could yield therapeutics with new properties that have the potential to treat both the inflammation and hyperresponsivesness associated with this disease.

Importance of fiberoptic bronchoscopy in identifying asthma phenotypes to direct personalized therapy

imagePurpose of review: This review summarizes the phenotyping of refractory asthma with an emphasis on how direct bronchoscopic observation and analysis of bronchoalveolar lavage (BAL), biopsy, and brushings of the airways helps direct specific personalized therapy. Additional testing used in phenotyping asthmatic patients is reviewed. Recent findings: Several studies and publications over the past decade have emphasized the importance of phenotyping refractory asthmatic patients to offer a better understanding of the pathobiology of disease. Bronchoscopy is a useful tool in phenotyping asthma with objective data obtained from BAL, endobronchial biopsy, and brushings. Phenotyping asthma with bronchoscopy affords personalized and successful therapy. Summary: By using fiberoptic bronchoscopy, specific asthma phenotypes can be identified: laryngopharyngeal reflux with silent aspiration; subacute bacterial infection; tissue eosinophilia; a combination of two or three of these; and nonspecific. Identifying these phenotypes and personalizing therapy with bronchoscopy leads to improved outcomes.

The role of inhaled corticosteroids in management of asthma in infants and preschoolers

imagePurpose of review: This review analyses published data on the treatment of wheezing in infants and preschoolers with inhaled corticosteroids (ICS), including the effect in subgroups of patients such as ‘multiple trigger wheeze’ and ‘episodic viral wheeze’. Recent findings: Therapy with ICS at daily doses of 100–200 μg results in significant clinical improvements in several outcomes in preschoolers and infants suspected of having asthma (multiple trigger wheeze). Such treatment is normally considered well tolerated. Although not well studied, higher daily doses may be associated with measurable effects on growth, which are not cumulative with continued treatment. In children who only wheeze in association with viral infections (episodic viral wheeze), preemptive treatment with high doses of ICS has demonstrated significant clinical effects on several outcomes, whereas lower doses seem to have little effect. Intermittent use of high doses of ICS has been associated with significant reductions in height and weight gain over 1 year. Summary: The review illustrates the complexity of treating wheezing in infants and preschoolers and interpreting the study results. It emphasizes the need for more studies in clinical subgroups, more long-term studies and dose–response studies to assess the optimal doses and safety of intermittent as well as regular ICS treatment.

Sleep-disordered breathing and childhood asthma: clinical implications

imagePurpose of review: Asthma morbidity in children remains high despite comprehensive evidence-based guidelines for evaluation and treatment. The objective of this review is to examine the evidence that obstructive sleep-disordered breathing often co-exists with asthma and is associated with asthma severity, and to discuss the clinical implications of this relationship, focusing particularly on studies published within the past year. Recent findings: Obstructive sleep-disordered breathing is highly prevalent in children with severe or poorly controlled asthma. Data from an observational study suggest that adenotonsillectomy markedly improves asthma outcomes in children with poorly controlled asthma and comorbid obstructive sleep apnea. Summary: Clinicians should consider evaluating and treating obstructive sleep-disordered breathing in children with severe or difficult-to-control asthma. Further controlled studies are needed to confirm that treatment of obstructive sleep apnea improves pediatric asthma outcomes, and to extend our understanding of how asthma and sleep-disordered breathing interact.

Noninvasive mechanical ventilation in patients having declined tracheal intubation.

Noninvasive mechanical ventilation in patients having declined tracheal intubation.

Intensive Care Med. 2012 Nov 27;

Authors: Azoulay E, Kouatchet A, Jaber S, Lambert J, Meziani F, Schmidt M, Schnell D, Mortaza S, Conseil M, Tchenio X, Herbecq P, Andrivet P, Guerot E, Lafabrie A, Perbet S, Camous L, Janssen-Langenstein R, Collet F, Messika J, Legriel S, Fabre X, Guisset O, Touati S, Kilani S, Alves M, Mercat A, Similowski T, Papazian L, Meert AP, Chevret S, Schlemmer B, Brochard L, Demoule A

Abstract
PURPOSE: Noninvasive ventilation (NIV) is a treatment option in patients with acute respiratory failure who are good candidates for intensive care but have declined tracheal intubation. The aim of our study was to report outcomes after NIV in patients with a do-not-intubate (DNI) order. METHODS: Prospective observational cohort study in all patients who received NIV for acute respiratory failure in 54 ICUs in France and Belgium, in 2010/2011. RESULTS: Goals of care, comfort, and vital status were assessed daily. On day 90, a telephone interview with patients and relatives recorded health-related quality of life (HRQOL), posttraumatic stress disorder-related symptoms, and symptoms of anxiety and depression. Post-ICU burden was compared between DNI patients and patients receiving NIV with no treatment-limitation decisions (TLD). Of 780 NIV patients, 574 received NIV with no TLD, and 134 had DNI orders. Hospital mortality was 44 % in DNI patients and 12 % in the no-TLD group. Mortality in the DNI group was lowest in COPD patients compared to other patients in the DNI group (34 vs. 51 %, P = 0.01). In the DNI group, HRQOL showed no significant decline on day 90 compared to baseline; day-90 data of patients and relatives did not differ from those in the no-TLD group. CONCLUSIONS: Do-not-intubate status was present among one-fifth of ICU patients who received NIV. DNI patients who were alive on day 90 experienced no decrease in HRQOL compared to baseline. The prevalences of anxiety, depression, and PTSD-related symptoms in these patients and their relatives were similar to those seen after NIV was used as part of full-code management (clinicaltrial.govNCT01449331).

PMID: 23184037 [PubMed - as supplied by publisher]

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