The role of the lung microbiome in the pathogenesis of idiopathic pulmonary fibrosis is unknown. We investigated whether unique microbial signatures were associated with progression of idiopathic ...pulmonary fibrosis.
Patients (aged 35-80 years) with idiopathic pulmonary fibrosis within 4 years of diagnosis from the Correlating Outcomes with biochemical Markers to Estimate Time-progression (COMET) in idiopathic pulmonary fibrosis study were followed up for a maximum of 80 weeks. Progression-free survival was defined as time to death, acute exacerbation, lung transplant, or decrease in forced vital capacity (FVC) of 10% or greater or decrease in diffusion capacity of the lung (DLCO) of 15% or greater. DNA was isolated from 55 samples of bronchoscopic alveolar lavage. 454 pyrosequencing was used to assign operational taxonomic units (OTUs) to bacteria based on a 3% sequence divergence. Adjusted Cox models were used to identify OTUs that were significantly associated with progression-free survival at a p<0.10. These OTUs were then used in the analysis of the principal components. The association between principal components and microbes with high factor loadings and progression-free survival were assessed with Cox regression analyses. The COMET study is registered with ClinicalTrials.gov, number NCT01071707.
Mean FVC was 70.1% (SD 17.0) and DLCO 42.3% (14.0) of predicted. Disease progression was significantly associated with increased relative abundance of two OTUs-Streptococcus OTU 1345 (relative risk 1.11, 95% CI 1.04-1.18; p=0.0009) and Staphylococcus OTU 1348 (1.16, 1.03-1.31, p=0.012). Thresholds for relative abundance of each OTU associated with progression-free survival were more than 3.9% for Streptococcus OTU 1345 (10.19, 2.94-35.35; p=0.0002) and more than 1.8% for Staphylococcus OTU 1348 (5.06, 1.71-14.93; p=0.003).
These preliminary data suggest progression of idiopathic pulmonary fibrosis is associated with the presence of specific members within the Staphylococcus and Streptococcus genera. Additional research will be needed to identify the specific bacterial species and to ascertain whether this is a causal association.
National Institutes of Health.
Impaired single breath carbon monoxide diffusing capacity (DLCO) is associated with emphysema. Small airways disease (SAD) may be a precursor lesion to emphysema, but the relationship between SAD and ...DLCO is undescribed. We hypothesized that in mild COPD, functional SAD (fSAD) defined by computed tomography (CT) and Parametric Response Mapping methodology would correlate with impaired DLCO. Using data from ever-smokers in the COPDGene cohort, we established that fSAD correlated significantly with lower DLCO among both non-obstructed and GOLD 1-2 subjects. The relationship between DLCO with CT-defined emphysema was present in all GOLD stages, but most prominent in severe disease. TRIAL REGISTRATION: NCT00608764. Registry: COPDGene. Registered 06 February 2008, retrospectively registered.
The benefits of triple therapy for chronic obstructive pulmonary disease (COPD) with an inhaled glucocorticoid, a long-acting muscarinic antagonist (LAMA), and a long-acting β
-agonist (LABA), as ...compared with dual therapy (either inhaled glucocorticoid-LABA or LAMA-LABA), are uncertain.
In this randomized trial involving 10,355 patients with COPD, we compared 52 weeks of a once-daily combination of fluticasone furoate (an inhaled glucocorticoid) at a dose of 100 μg, umeclidinium (a LAMA) at a dose of 62.5 μg, and vilanterol (a LABA) at a dose of 25 μg (triple therapy) with fluticasone furoate-vilanterol (at doses of 100 μg and 25 μg, respectively) and umeclidinium-vilanterol (at doses of 62.5 μg and 25 μg, respectively). Each regimen was administered in a single Ellipta inhaler. The primary outcome was the annual rate of moderate or severe COPD exacerbations during treatment.
The rate of moderate or severe exacerbations in the triple-therapy group was 0.91 per year, as compared with 1.07 per year in the fluticasone furoate-vilanterol group (rate ratio with triple therapy, 0.85; 95% confidence interval CI, 0.80 to 0.90; 15% difference; P<0.001) and 1.21 per year in the umeclidinium-vilanterol group (rate ratio with triple therapy, 0.75; 95% CI, 0.70 to 0.81; 25% difference; P<0.001). The annual rate of severe exacerbations resulting in hospitalization in the triple-therapy group was 0.13, as compared with 0.19 in the umeclidinium-vilanterol group (rate ratio, 0.66; 95% CI, 0.56 to 0.78; 34% difference; P<0.001). There was a higher incidence of pneumonia in the inhaled-glucocorticoid groups than in the umeclidinium-vilanterol group, and the risk of clinician-diagnosed pneumonia was significantly higher with triple therapy than with umeclidinium-vilanterol, as assessed in a time-to-first-event analysis (hazard ratio, 1.53; 95% CI, 1.22 to 1.92; P<0.001).
Triple therapy with fluticasone furoate, umeclidinium, and vilanterol resulted in a lower rate of moderate or severe COPD exacerbations than fluticasone furoate-vilanterol or umeclidinium-vilanterol in this population. Triple therapy also resulted in a lower rate of hospitalization due to COPD than umeclidinium-vilanterol. (Funded by GlaxoSmithKline; IMPACT ClinicalTrials.gov number, NCT02164513 .).
Chronic obstructive pulmonary disease (COPD) is currently a leading cause of death worldwide, and its burden is expected to rise in the coming years. Common COPD symptoms include dyspnea, cough ...and/or sputum production. Some patients may experience acute worsening of symptoms (known as an exacerbation), and therefore require additional therapy. Exacerbations are mainly triggered by respiratory infections and environmental factors. Healthcare professionals face many challenges in COPD management, including the heterogeneity of the disease and under-reporting of symptoms. The authors review these challenges and provide recommendations for the best methods to assess COPD. The goals of COPD treatment include recognising the impact that both symptoms and exacerbations have on patients’ lives when considering optimal patient-focused management. The review discusses the need for COPD management strategies to include both pharmacologic and non-pharmacologic approaches and provides recommendations for monitoring treatment outcomes and adjusting management strategies accordingly. Novel treatment strategies including precision medicine and point-of-care testing are also discussed.
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•Challenges of COPD management include disease heterogeneity and under-diagnosis.•The best available tools should be used for COPD diagnosis and assessment.•Optimal management of COPD includes recognizing both symptoms and exacerbations.•Both pharmacologic and non-pharmacologic treatment strategies should be considered.•Novel strategies (e.g. precision medicine, point-of-care testing) may be of value.
The aim of this study is to identify genetic loci associated with post-bronchodilator FEV
/FVC and FEV
, and develop a multi-gene predictive model for lung function in COPD.
Genome-wide association ...study (GWAS) of post-bronchodilator FEV
/FVC and FEV
was performed in 1645 non-Hispanic White European descent smokers.
A functional rare variant in SERPINA1 (rs28929474: Glu342Lys) was significantly associated with post-bronchodilator FEV
/FVC (p = 1.2 × 10
) and FEV
(p = 2.1 × 10
). In addition, this variant was associated with COPD (OR = 2.3; p = 7.8 × 10
) and severity (OR = 4.1; p = 0.0036). Heterozygous subjects (CT genotype) had significantly lower lung function and higher percentage of COPD and more severe COPD than subjects with the CC genotype. 8.6% of the variance of post-bronchodilator FEV
/FVC can be explained by SNPs in 10 genes with age, sex, and pack-years of cigarette smoking (P < 2.2 × 10
).
This study is the first to show genome-wide significant association of rs28929474 in SERPINA1 with lung function. Of clinical importance, heterozygotes of rs28929474 (4.7% of subjects) have significantly reduced pulmonary function, demonstrating a major impact in smokers. The multi-gene model is significantly associated with CT-based emphysema and clinical outcome measures of severity. Combining genetic information with demographic and environmental factors will further increase the predictive power for assessing reduced lung function and COPD severity.
From GOLD 0 to Pre-COPD Han, MeiLan K; Agusti, Alvar; Celli, Bartolome R ...
American journal of respiratory and critical care medicine,
02/2021, Letnik:
203, Številka:
4
Journal Article
PDF
