Lower Airway Dysbiosis Augments Lung Inflammatory Injury in Mild-to-Moderate Chronic Obstructive Pulmonary Disease.

Rationale: Chronic obstructive pulmonary disease (COPD) is associated with high morbidity, mortality, and healthcare costs. Cigarette smoke is a causative factor; however, not all heavy smokers develop COPD. Microbial colonization and infections are contributing factors to disease progression in advanced stages. Objectives: We investigated whether lower airway dysbiosis occurs in mild-to-moderate COPD and analyzed possible mechanistic contributions to COPD pathogenesis. Methods: We recruited 57 patients with a >10 pack-year smoking history: 26 had physiological evidence of COPD, and 31 had normal lung function (smoker control subjects). Bronchoscopy sampled the upper airways, lower airways, and environmental background. Samples were analyzed by 16S rRNA gene sequencing, whole genome, RNA metatranscriptome, and host RNA transcriptome. A preclinical mouse model was used to evaluate the contributions of cigarette smoke and dysbiosis on lower airway inflammatory injury. Measurements and Main Results: Compared with smoker control subjects, microbiome analyses showed that the lower airways of subjects with COPD were enriched with common oral commensals. The lower airway host transcriptomics demonstrated differences in markers of inflammation and tumorigenesis, such as upregulation of IL-17, IL-6, ERK/MAPK, PI3K, MUC1, and MUC4 in mild-to-moderate COPD. Finally, in a preclinical murine model exposed to cigarette smoke, lower airway dysbiosis with common oral commensals augments the inflammatory injury, revealing transcriptomic signatures similar to those observed in human subjects with COPD. Conclusions: Lower airway dysbiosis in the setting of smoke exposure contributes to inflammatory injury early in COPD. Targeting the lower airway microbiome in combination with smoking cessation may be of potential therapeutic relevance.

The role of the respiratory microbiome in asthma.

Asthma is a common airways disease and the human microbiome plays an increasingly recognised role in asthma pathogenesis. Furthermore, the respiratory microbiome varies with asthma phenotype, endotype and disease severity. Consequently, asthma therapies have a direct effect on the respiratory microbiome. Newer biological therapies have led to a significant paradigm shift in how we treat refractory Type 2 high asthma. While airway inflammation is the generally accepted mechanism of action of all asthma therapies, including both inhaled and systemic therapies, there is evidence to suggest that they may also alter the microbiome to create a more functionally balanced airway microenvironment while also influencing airway inflammation directly. This downregulated inflammatory cascade seen biochemically, and reflected in improved clinical outcomes, supports the hypothesis that biological therapies may in fact affect the microbiome-host immune system dynamic and thus represent a therapeutic target for exacerbations and disease control.

A clinicians' review of the respiratory microbiome.

The respiratory microbiome and its impact in health and disease is now well characterised. With the development of next-generation sequencing and the use of other techniques such as metabolomics, the functional impact of microorganisms in different host environments can be elucidated. It is now clear that the respiratory microbiome plays an important role in respiratory disease. In some diseases, such as bronchiectasis, examination of the microbiome can even be used to identify patients at higher risk of poor outcomes. Furthermore, the microbiome can aid in phenotyping. Finally, development of multi-omic analysis has revealed interactions between the host and microbiome in some conditions. This review, although not exhaustive, aims to outline how the microbiome is investigated, the healthy respiratory microbiome and its role in respiratory disease. Educational aims: To define the respiratory microbiome and describe its analysis.To outline the respiratory microbiome in health and disease.To describe future directions for microbiome research.

Air Travel for Subjects Receiving Long-Term Oxygen Therapy.

BACKGROUND: Ambulatory oxygen (O2) is the recommended treatment for hypoxemia at rest or induced by exercise. Commercial aircraft often fly at altitudes of 30,000 feet; their cabins are pressurized to altitudes of 6,000-8,000 feet, with an equivalent FIO2 of 0.15. O2 supplementation, for those receiving baseline ambulatory O2, is paramount. METHODS: We gathered information on subjects' experience traveling with supplementary oxygen and reasons individuals receiving O2 do not travel. Subjects were identified using a home oxygen database. Data were gathered by postal questionnaire. The objective of this study was to gather information relevant to subjects' experience organizing travel with supplementary oxygen and their experience of traveling itself. RESULTS: Between 2013 and 2015, 512 patients were entered into the database: 277 were excluded (269 had died, 8 had incomplete records). We sent 235 questionnaires, and 50 responses were received (21% response rate). Of these, 11 (22%) were returned as the patient had died, 20 (40%) had not traveled by air, 11 (22%) had flown with O2, 4 (8%) no longer used O2, and 4 (8%) forms were incomplete. Of those who traveled with O2, 54% found it complicated to organize their trip, 72% found it complicated to access information, and 81% would fly again. Regarding those who had never flown with O2, 35% were unaware that O2 was available on commercial aircraft, 30% had no wish to travel, and 30% had worries regarding their health. CONCLUSIONS: Air travel is challenging; however, those who did travel reported a mainly positive experience. Increasing available information on options for travel should help individuals.