The lung is a complex ecosystem of host cells and microbes often disrupted in pathological conditions. Although bacteria have been hypothesized as agents of carcinogenesis, little is known about microbiota profile of the most prevalent cancer subtypes: adenocarcinoma (ADC) and squamous cell carcinoma (SCC). To characterize lung cancer (LC) microbiota a first a screening was performed through a pooled sequencing approach of 16S ribosomal RNA gene (V3-V6) using a total of 103 bronchoalveaolar lavage fluid samples. Then, identified taxa were used to inspect 1009 cases from The Cancer Genome Atlas and to annotate tumor unmapped RNAseq reads. Microbial diversity was analyzed per cancer subtype, history of cigarette smoking and airflow obstruction, among other clinical data. We show that LC microbiota is enriched in Proteobacteria and more diverse in SCC than ADC, particularly in males and heavier smokers. High frequencies of Proteobacteria were found to discriminate a major cluster, further subdivided into well-defined communities’ associated with either ADC or SCC. Here, a SCC subcluster differing from other cases by a worse survival was correlated with several Enterobacteriaceae. Overall, this study provides first evidence for a correlation between lung microbiota and cancer subtype and for its influence on patient life expectancy.

Lung cancer configures as one of the deadliest types of cancer. The future implementation of early screening methods such as exhaled breath condensate analysis and low dose computed tomography (CT) as an alternative to current chest imaging based screening will lead to an increased burden on bronchoscopy units. New approaches for improvement of diagnosis in bronchoscopy units, regarding patient management, are likely to have clinical impact in the future. Diagnostic approaches to address mortality of lung cancer include improved early detection and stratification of the cancers according to its prognosis and further response to drug treatment. In this study, we performed a detailed mass spectrometry based proteome analysis of acellular bronchoalveolar lavage (BAL) fluid samples on an observational prospective cohort consisting of 90 suspected lung cancer cases which were followed during two years. The thirteen new lung cancer cases diagnosed during the follow up time period clustered, based on liquid chromatography-mass spectrometry (LC-MS) data, with lung cancer cases at the time of BAL collection. Hundred and thirty-tree potential biomarkers were identified showing significantly differential expression when comparing lung cancer versus non-lung cancer. The regulated biomarkers showed a large overlap with biomarkers detected in tissue samples.

Acellular bronchoalveolar lavage (BAL) proteomics can partially separate lung cancer from non-lung cancer patients based on principal component analysis and multivariate analysis. Furthermore, the variance in the proteomics data sets is correlated mainly with lung cancer status and, to a lesser extent, smoking status and gender. Despite these advances BAL small and large extracellular vehicles (EVs) proteomes reveal aberrant protein expression in paracrine signaling mechanisms in cancer initiation and progression. We consequently present a case-control study of 24 bronchoalveolar lavage extracellular vesicle samples which were analyzed by state-of-the-art liquid chromatography-mass spectrometry (LC-MS). We obtained evidence that BAL EVs proteome complexity correlated with lung cancer stage 4 and mortality within two years´ follow-up (p value = 0.006). The potential therapeutic target DNMT3B complex is significantly up-regulated in tumor tissue and BAL EVs. The computational analysis of the immune and fibroblast cell markers in EVs suggests that patients who deceased within the follow-up period display higher marker expression indicative of innate immune and fibroblast cells (four out of five cases). This study provides insights into the proteome content of BAL EVs and their correlation to clinical outcomes.

The lung is inhabited by a diverse microbiome that originates from the oropharynx by a mechanism of micro-aspiration. Its bacterial biomass is usually low; however, this condition shifts in lung cancer (LC), chronic obstructive pulmonary disease (COPD) and interstitial lung disease (ILD). These chronic lung disorders (CLD) may coexist in the same patient as comorbidities and share common risk factors, among which the microbiome is included. We characterized the microbiome of 106 bronchoalveolar lavages. Samples were initially subdivided into cancer and non-cancer and high-throughput sequenced for the 16S rRNA gene. Additionally, we used a cohort of 25 CLD patients where crossed comorbidities were excluded. Firmicutes, Proteobacteria and Bacteroidetes were the most prevalent phyla independently of the analyzed group. Streptococcus and Prevotella were associated with LC and Haemophilus was enhanced in COPD versus ILD. Although no significant discrepancies in microbial diversity were observed between cancer and non-cancer samples, statistical tests suggested a gradient across CLD where COPD and ILD displayed the highest and lowest alpha diversities, respectively. Moreover, COPD and ILD were separated in two clusters by the unweighted UniFrac distance (P value = 0.0068). Our results support the association of Streptoccocus and Prevotella with LC and of Haemophilus with COPD, and advocate for specific CLD signatures.

There is a high mortality rate in late-stage patients with COPD. The most relevant factors associated with mortality were lung cancer, respiratory failure and noninvasive ventilation, severe exacerbations with hospitalization, and lower functional exercise capacity.

Introduction Continuous positive airway pressure is an effective treatment for obstructive sleep apnoea syndrome. However, positive airway pressure compliance rates are disappointingly low, so effective interventions are needed to improve compliance in sleep apnoea. Telemonitoring has been used to improve compliance, but results have been inconsistent. This study aimed to determine outcomes of telemonitoring positive airway pressure compliance and efficacy data compared to usual care and phone-call care. Methods Randomized controlled study in which 51 patients (82.4% male; between 25 and 78 years), diagnosed with moderate to severe obstructive sleep apnoea were consecutively randomized to usual care, weekly phone-call care or telemonitored care with the use of Restraxx™. All patients were submitted to a comprehensive educational programme during positive airway pressure adaptation. Patients were followed for the first four weeks of treatment with automatic positive airway pressure (AutoSet Spirit S8®; ResMed), and compliance and efficacy data were analyzed. Results Telemonitored care group used automatic positive airway pressure an average of 5.0 ± 1.8 hours/night, usual care patients 5.1 ± 2.5 hours and phone-call care patients 3.9 ± 2.6 hours. The residual Apnoea--Hypopnoea Index was 5.3 ± 3.0 in telemonitored care, 5.0 ± 2.5 in usual care and 5.6 ± 3.8 in phone-call care. No statistically significant differences were found between groups regarding positive airway pressure compliance or efficacy ( p = 0.296 and p = 0.825, respectively). Discussion In the presence of a comprehensive educational programme during positive airway pressure adaptation, telemonitoring patients did not show benefits concerning compliance and efficacy. A larger follow-up period is needed to evaluate the long-term results of a telemonitoring programme.

Pulmonary mucormycosis is an emergent and life-threatening invasive fungal infection underdiagnosed by clinicians due to unspecific clinical picture and lack of awareness. Although the acknowledgment of risk factors, clinical and radiological findings may increase early recognition, the definite diagnosis is challenging to establish and the ideal treatment has never been delineated. The authors describe a rare case of pulmonary mucormycosis that was successfully treated with dual antifungal treatment and surgery in a patient with uncontrolled diabetes. When last evaluated, he was asymptomatic with no evidence of relapse. To our knowledge this is a rare report of a successfully treated diabetic patient with pulmonary mucormycosis with LAmB , triazole posaconazole and surgery with no evidence of recurrence. We highlight the importance of clinicians' awareness to early diagnosis, combined antifungal treatment and adjuvant surgery as the greatest chance of cure of a rapidly progressive disease with high mortality and morbidity.

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