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.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Celli et al discuss the need to revise the definition and nomenclature of chronic obstructive pulmonary disease. The definition and the diagnostic criteria (terms often mixed or confused) of a ...disease represent different constructs. A definition must describe its essential attributes while avoiding circularity, it must also not consist of terms that are synonymous with it. It should not be too wide or too narrow (not miss or include anything to which the term should not be applied). It should also be clear, understandable, and positive, attempting to avoid concepts derived by exclusions.
The frequency of COPD exacerbations during treatment with a triple inhaler — delivering a long-acting beta-agonist (LABA), a long-acting muscarinic antagonist (LAMA), and an inhaled glucocorticoid — ...was compared with that with a LABA–LAMA or LABA–inhaled glucocorticoid.
Executive summary of the Global Strategy for Prevention, Diagnosis and Management of COPD 2023: the latest evidence-based strategy document from the Global Initiative for Chronic Obstructive Lung ...Disease (GOLD
)
https://bit.ly/3KCaTGe
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.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
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
Recenzirano
Odprti dostop
Han et al discuss Global Initiative for Chronic Obstructive Lung Disease (GOLD) report and pre-chronic obstructive pulmonary disease (Pre-COPD). The diagnosis of chronic obstructive pulmonary disease ...(COPD) currently requires the demonstration of poorly reversible airflow limitation, defined as a post-bronchodilator FEV1/FVC <0.7. Although some have argued that the lower limit of normal rather than a fixed value to define obstruction may be more accurate and theoretically more appropriate, recent pooled data from multiple NIH cohorts demonstrate that the fixed FEV1/FVC ratio <0.70 provides discrimination of COPD-related hospitalization and mortality that is equal to or better than other thresholds and the lower limit of normal.
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