Nasal biomarkers of immune function differ based on smoking and respiratory disease status.

Respiratory biomarkers have the potential to identify airway injury by revealing inflammatory processes within the respiratory tract. Currently, there are no respiratory biomarkers suitable for clinical use to identify patients that warrant further diagnostic work-up, counseling, and treatment for toxic inhalant exposures or chronic airway disease. Using a novel, noninvasive method of sampling the nasal epithelial lining fluid, we aimed to investigate if nasal biomarker patterns could distinguish healthy nonsmoking adults from active smokers and those with chronic upper and lower airway disease in this exploratory study. We compared 28 immune mediators from healthy nonsmoking adults (n = 32), former smokers with COPD (n = 22), chronic rhinosinusitis (CRS) (n = 22), and smoking adults without airway disease (n = 13). Using ANOVA, multinomial logistic regressions, and weighted gene co-expression network analysis (WGCNA), we determined associations between immune mediators and each cohort. Six mediators (IL-7, IL-10, IL-13, IL-12p70, IL-15, and MCP-1) were lower among disease groups compared to healthy controls. Participants with lower levels of IL-10, IL-12p70, IL-13, and MCP-1 in the nasal fluid had a higher odds of being in the COPD or CRS group. The cluster analysis identified groups of mediators that correlated with disease status. Specifically, the cluster of IL-10, IL-12p70, and IL-13, was positively correlated with healthy and negatively correlated with COPD groups, and two clusters were correlated with active smoking. In this exploratory study, we preliminarily identified groups of nasal mucosal mediators that differed by airway disease and smoking status. Future prospective, age-matched studies that control for medication use are needed to validate these patterns and determine if nasosorption has diagnostic utility for upper and lower airway disease or injury.

Differences of the Nasal Microbiome and Mycobiome by Clinical Characteristics of COPD Patients.

Rationale: While studies suggest that the lung microbiome may influence risk of chronic obstructive pulmonary disease (COPD) exacerbations, little is known about the relationship between the nasal biome and clinical characteristics of COPD patients. Methods: We sampled the nasal lining fluid by nasosorption of both nares of 20 people with moderate-to-severe COPD. All 40 samples, plus 4 negative controls, underwent DNA extraction, and 16SV4 ribosomal RNA (rRNA) (bacterial) and ribosomal internal transcribed spacer 2 (ITS2) (fungal) sequencing. We measured the proportion of variance (R2) in beta diversity explained by clinical factors, including age, sex, body mass index (BMI), COPD treatment, disease severity (forced expiratory volume in 1 second [FEV1], symptom/exacerbation frequency), peripheral eosinophil level (≥150 versus <150 cells/µL) and season of sampling, with the PERMANOVA test on the Bray-Curtis dissimilarities, accounting for within-person correlation of samples. We assessed the relative abundance of microbial features in the nasal community and their associations with clinical characteristics using the Microbiome Multivariable Association with Linear Models (MaAsLin2) package. Results: The most abundant nasal fluid bacterial taxa were Corynebacterium, Staphylococcus, Streptococcus, Moraxella, and Dolosigranulum, and fungal taxa were Malassezia, Candida, Malasseziales, Cladosporium and Aspergillus. Bacterial microbiome composition was associated with short-acting muscarinic antagonist use (R2 11.8%, p=0.002), sex (R2 8.3%, p=0.044), nasal steroid use (R2 7.7%, p=0.064), and higher eosinophil level (R2 7.6%, p=0.084). Mycobiome composition was associated with higher eosinophil level (R2 14.4%, p=0.004) and low FEV1 (R2 7.5%, p=0.071). No specific bacterium or fungus differed significantly in relative abundance by clinical characteristics in the multivariate per-feature analysis. Conclusion: The taxonomical composition of the nasal biome is heterogeneous in COPD patients and may be explained in part by clinical characteristics.

Change in Inhaler Use, Lung Function, and Oxygenation in Association with Symptoms in COPD.

Despite clinical guidelines for chronic obstructive pulmonary disease (COPD) patients to self-treat worsening respiratory symptoms with supplemental inhaler/nebulizer use, few studies have investigated if symptom changes are associated with differences in oxygenation, lung function, or self-treatment. A total of 26 former smokers (mean age 72.7 ±7.5 years; 57.7% female) with COPD (≥ Global Initiative for Chronic Obstructive Lung Disease Stage 2) were followed for up to 4 months, during which they recorded daily oxygenation, lung function, and inhaler/nebulizer use. Differences in these health measures were assessed in association with self-reported worsening symptoms and COPD exacerbations, as defined by validated questionnaire. We collected 2451 observations with spirometry and questionnaire data and identified 253 symptom days (10.3%) and 47 (1.92%) exacerbation days. In linear mixed effects models adjusted for age, sex, race, height, weight, and season, each respiratory symptom reported worse than baseline was associated with a 0.19 percentage point (95% CI -0.31 to -0.07) lower daily oxygen saturation (p=0.002). On major symptom days (defined as worse-than-baseline dyspnea, sputum purulence or sputum amount), oxygen saturation was 0.56 percentage points lower (95% CI -0.89 to -0.23, p=0.001) than days without increased major symptoms. We found no association of symptom days or exacerbations with forced expiratory volume in 1 second. There were 8 reports of increased inhaler/nebulizer use from baseline on symptom days (1.5% of 253). In this moderate-to-severe COPD population, worsening respiratory symptoms were common and associated with lower oxygenation. However, participants did not self-treat symptoms with increased inhaler/nebulizer use, which may suggest poor perceived clinical benefit from short-acting bronchodilators and a potential target for patient education.