Managing asthma in adolescents and adults 2020 asthma guideline update From the National Asthma Education and Prevention Program

Asthma is a major public health problem worldwide and is associated with excess morbidity, mortality, and economic costs associated with lost productivity. The National Asthma Education and Prevention Program has released the 2020 Asthma Guideline Update with updated evidence-based recommendations for treatment of patients with asthma. To report updated recommendations for 6 topics for clinical management of adolescents and adults with asthma: (1) intermittent inhaled corticosteroids (ICSs); (2) add-on long-acting muscarinic antagonists; (3) fractional exhaled nitric oxide; (4) indoor allergen mitigation; (5) immunotherapy; and (6) bronchial thermoplasty. The National Heart, Lung, and Blood Advisory Council chose 6 topics to update the 2007 asthma guidelines based on results from a 2014 needs assessment. The Agency for Healthcare Research and Quality conducted systematic reviews of these 6 topics based on literature searches up to March-April 2017. Reviews were updated through October 2018 and used by an expert panel (n = 19) that included asthma content experts, primary care clinicians, dissemination and implementation experts, and health policy experts to develop 19 new recommendations using the GRADE method. The 17 recommendations for individuals aged 12 years or older are reported in this Special Communication. From 20 572 identified references, 475 were included in the 6 systematic reviews to form the evidence basis for these recommendations. Compared with the 2007 guideline, there was no recommended change in step 1 (intermittent asthma) therapy (as-needed short-acting ß2-agonists [SABAs] for rescue therapy). In step 2 (mild persistent asthma), either daily low-dose ICS plus as-needed SABA therapy or as-needed concomitant ICS and SABA therapy are recommended. Formoterol in combination with an ICS in a single inhaler (single maintenance and reliever therapy) is recommended as the preferred therapy for moderate persistent asthma in step 3 (low-dose ICS-formoterol therapy) and step 4 (medium-dose ICS-formoterol therapy) for both daily and as-needed therapy. A short-term increase in the ICS dose alone for worsening of asthma symptoms is not recommended. Add-on long-acting muscarinic antagonists are recommended in individuals whose asthma is not controlled by ICS-formoterol therapy for step 5 (moderate-severe persistent asthma). Fractional exhaled nitric oxide testing is recommended to assist in diagnosis and monitoring of symptoms, but not alone to diagnose or monitor asthma. Allergen mitigation is recommended only in individuals with exposure and relevant sensitivity or symptoms. When used, allergen mitigation should be allergen specific and include multiple allergen-specific mitigation strategies. Subcutaneous immunotherapy is recommended as an adjunct to standard pharmacotherapy for individuals with symptoms and sensitization to specific allergens. Sublingual immunotherapy is not recommended specifically for asthma. Bronchial thermoplasty is not recommended as part of standard care; if used, it should be part of an ongoing research effort. Asthma is a common disease with substantial human and economic costs globally. Although there is no cure or established means of prevention, effective treatment is available. Use of the recommendations in the 2020 Asthma Guideline Update should improve the health of individuals with asthma.

Prevalence of hiatal hernia by blinded multidetector CT in patients with idiopathic pulmonary fibrosis.

Hiatal hernia (HH) is associated with gastro-oesophageal reflux (GOR) and/or GOR disease and may contribute to idiopathic pulmonary fibrosis (IPF). We hypothesised that HH evaluated by computed tomography is more common in IPF than in asthma or chronic obstructive pulmonary disease (COPD), and correlates with abnormal GOR measured by pH probe testing. Rates of HH were compared in three cohorts, IPF (n=100), COPD (n=60) and asthma (n=24), and evaluated for inter-observer agreement. In IPF, symptoms and anti-reflux medications were correlated with diffusing capacity of the lung for carbon monoxide (D(L,CO)) and composite physiologic index (CPI). HH was correlated with pH probe testing in IPF patients (n=14). HH was higher in IPF (39%) than either COPD (13.3%, p=0.00009) or asthma (16.67%, p=0.0139). The HH inter-observer κ agreement was substantial in IPF (κ=0.78) and asthma (κ=0.86), and moderate in COPD (κ=0.42). In IPF, HH did not correlate with lung function, except in those on anti-reflux therapy, who had a better D(L,CO) (p<0.03) and CPI (p<0.04). HH correlated with GOR as measured by DeMeester scores (p<0.04). HH is more common in IPF than COPD or asthma. In an IPF cohort, HH correlated with higher DeMeester scores, confirming abnormal acid GOR. Presence of HH alone was not associated with decreased lung function.

Prioritizing comparative-effectiveness research topics via stakeholder involvement: an application in COPD.

A major priority for funding agencies and researchers involved in comparative-effectiveness research (CER) is to ensure that research questions will produce findings that are relevant and feasible to implement. In this article, we describe a process for involving experts and stakeholders in identifying and prioritizing CER studies, as illustrated by our experience in chronic obstructive pulmonary disease (COPD).

Systematic review of the association between lung function and Type 2 diabetes mellitus.

AIMS: To describe the association between lung function and Type 2 diabetes mellitus. METHODS: We identified English language studies evaluating the association between lung function and diabetes mellitus in the MEDLINE database from 1 January 1975 to 31 December 2009. We evaluated study quality based on established criteria (54 studies were reviewed, 34 met the inclusion criteria). RESULTS: Cross-sectional studies showed that adults with diabetes mellitus have lower forced vital capacity (FVC) and forced expiratory volume in one second (FEV1), with reductions in FVC more consistent than FEV1 and lower diffusion capacity (DLCO) compared with their non-diabetic counterparts. The reduced lung function in patients with diabetes is inversely related to blood glucose levels, duration of diabetes and its severity and is independent of smoking or obesity. Findings in cohort studies have been less consistent, with only a few studies identifying an increased rate of lung function decline in adults with diabetes. In addition, other cohort studies have reported an association between decreased lung function and incident insulin resistance and diabetes. Studies evaluating biological mechanisms to explain the association between lung impairment and diabetes identified microangiopathy of the alveolar capillaries and pulmonary arterioles, chronic inflammation, autonomic neuropathy involving the respiratory muscles, loss of elastic recoil secondary to collagen glycosylation of lung parenchyma, hypoxia-induced insulin resistance and low birthweight, as being associated with both insulin resistance and impaired lung function. CONCLUSIONS: There is an association between diabetes mellitus and decreased lung function, but the definitive direction as well as the exact pathophysiological mechanism to explain this association requires further investigation.

CPAP and survival in moderate-to-severe obstructive sleep apnoea syndrome and hypoxaemic COPD.

Obstructive sleep apnoea syndrome (OSAS) often coexists in patients with chronic obstructive pulmonary disease (COPD). The present prospective cohort study tested the effect of OSAS treatment with continuous positive airway pressure (CPAP) on the survival of hypoxaemic COPD patients. It was hypothesised that CPAP treatment would be associated with higher survival in patients with moderate-to-severe OSAS and hypoxaemic COPD receiving long-term oxygen therapy (LTOT). Prospective study participants attended two outpatient advanced lung disease LTOT clinics in São Paulo, Brazil, between January 1996 and July 2006. Of 603 hypoxaemic COPD patients receiving LTOT, 95 were diagnosed with moderate-to-severe OSAS. Of this OSAS group, 61 (64%) patients accepted and were adherent to CPAP treatment, and 34 did not accept or were not adherent and were considered not treated. The 5-yr survival estimate was 71% (95% confidence interval 53-83%) and 26% (12-43%) in the CPAP-treated and nontreated groups, respectively (p<0.01). After adjusting for several confounders, patients treated with CPAP showed a significantly lower risk of death (hazard ratio of death versus nontreated 0.19 (0.08-0.48)). The present study found that CPAP treatment was associated with higher survival in patients with moderate-to-severe OSAS and hypoxaemic COPD receiving LTOT.

Treatment of venous thromboembolism with low-molecular-weight heparin: a synthesis of the evidence published in systematic literature reviews.

OBJECTIVE: To evaluate the methodology and cumulative evidence presented in systematic reviews of clinical trials comparing low-molecular-weight heparin (LMWH) with unfractionated heparin (UFH) for the treatment of venous thromboembolism. METHODS: We reviewed all systematic reviews of clinical trials published until March 2002. Fourteen systematic literature reviews were published between 1994 and 2000. Deficiencies in methodological quality were common, particularly in the description of search strategies, assessment of clinical trial quality, and methods used to combine results. RESULTS: Results of reviews indicate that LMWH is superior to UFH for the treatment of venous thromboembolism, particularly in reducing mortality. Patients with isolated deep venous thrombosis or deep venous thrombosis with concomitant pulmonary embolism seemed to have similar benefit. However, the benefits of LMWH over UFH were smaller in magnitude in reviews that included more recent clinical trials.

Patterns and significance of exhaled-breath biomarkers in lung transplant recipients with acute allograft rejection.

BACKGROUND: Obliterative bronchiolitis (OB) remains one of the leading causes of death in lung transplant recipients after 2 years, and acute rejection (AR) of lung allograft is a major risk factor for OB. Treatment of AR may reduce the incidence of OB, although diagnosis of AR often requires bronchoscopic lung biopsy. In this study, we evaluated the utility of exhaled-breath biomarkers for the non-invasive diagnosis of AR. METHODS: We obtained breath samples from 44 consecutive lung transplant recipients who attended ambulatory follow-up visits for the Johns Hopkins Lung Transplant Program. Bronchoscopy within 7 days of their breath samples showed histopathology in 21 of these patients, and we included them in our analysis. We measured hydrocarbon markers of pro-oxidant events (ethane and 1-pentane), isoprene, acetone, and sulfur-containing compounds (hydrogen sulfide and carbonyl sulfide) in exhaled breath and compared their levels to the lung histopathology, graded as stable (non-rejection) or AR. None of the study subjects were diagnosed with OB or infection at the time of the clinical bronchoscopy. RESULTS: We found no significant difference in exhaled levels of hydrocarbons, acetone, or hydrogen sulfide between the stable and AR groups. However, we did find significant increase in exhaled carbonyl sulfide (COS) levels in AR subjects compared with stable subjects. We also observed a trend in 7 of 8 patients who had serial sets of breath and histopathology data that supported a role for COS as a breath biomarker of AR. CONCLUSIONS: This study demonstrated elevations in exhaled COS levels in subjects with AR compared with stable subjects, suggesting a diagnostic role for this non-invasive biomarker. Further exploration of breath analysis in lung transplant recipients is warranted to complement fiberoptic bronchoscopy and obviate the need for this procedure in some patients.

Race and sex differences in consistency of care with national asthma guidelines in managed care organizations.

BACKGROUND: In the United States, morbidity from asthma disproportionately affects African Americans and women. Although inadequate care contributes to overall asthma morbidity, less is known about differences in asthma care by race and sex. SUBJECTS AND METHODS: To examine the relationships of race and sex with asthma care, we analyzed responses to questionnaires administered to adults enrolled in 16 managed care organizations participating in the Outcomes Management System Asthma Study between September and December 1993. Indicators of care consistent with National Asthma Education and Prevention Program (1991) recommendations were assessed. Of a random sample of 8640 patients asked to participate, 6612 (77%) completed the survey. This study focused on 5062 (14% African American, 72% women) patients with at least moderate asthma symptom severity. RESULTS: Fewer African Americans than whites reported care consistent with recommendations for medication use (eg, daily inhaled corticosteroid use, 34.9% vs 54.4%; P =.001), self-management education (eg, action plan, 42.0% vs 53.8%; P =.001), avoiding triggers (37.6% vs 53.6%; P =.001), and specialist care (28.3% vs 41.0%; P =.001). Differences in asthma care by sex were smaller and tended to favor women except for daily inhaled corticosteroid use (women vs men: 49.6% vs 58.3%; P =.001) and having specialist care (37.7% vs 43.1%; P =.001). Similar race and sex differences were observed after adjusting for age, education, employment, and symptom frequency. CONCLUSIONS: Even among patients with health insurance, disparities in asthma care for African Americans compared with whites exist and may contribute to race disparities in outcomes. Women generally reported better asthma care but may benefit from greater use of inhaled corticosteroids.

High-frequency ventilation for acute lung injury and ARDS.

In patients with acute lung injury (ALI) and ARDS, conventional mechanical ventilation (CV) may cause additional lung injury from overdistention of the lung during inspiration, repeated opening and closing of small bronchioles and alveoli, or from excessive stress at the margins between aerated and atelectatic lung regions. Increasing evidence suggests that smaller tidal volumes (VTs) and higher end-expiratory lung volumes (EELVs) may be protective from these forms of ventilator-associated lung injury and may improve outcomes from ALI/ARDS. High-frequency ventilation (HFV)-based ventilatory strategies offer two potential advantages over CV for patients with ALI/ARDS. First, HFV uses very small VTs, allowing higher EELVs with less overdistention than is possible with CV. Second, despite the small VTs, high respiratory rates during HFV allow the maintenance of normal or near-normal PaCO2 levels. In this review, the use of HFV as a lung protective strategy for patients with ALI/ARDS is discussed.