Comparative analysis of the bronchoalveolar microbiome in Portuguese patients with different chronic lung disorders.

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.

Profiling of lung microbiota discloses differences in adenocarcinoma and squamous cell carcinoma.

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.

Can we change a genetically determined future?

We describe the clinical evolution of the first patient diagnosed with a severe α-1 antitrypsin (AAT) deficiency caused by a rare null allele (Q0Ourém), over the past 18 years. We highlight the clinical course of the disease as well as the evolution of the pulmonary function tests from initial diagnosis and the benefits of augmentation therapy for this specific condition. We report the case of a 43-year-old man with exertion dyspnoea who was observed in our pulmonology unit. The unexpected findings in the complementary examinations led us to diagnose AAT deficiency and to the discovery of a new mutation with the SERPIN A1 gene (hence named Q0Ourém) responsible for the disease. Augmentation therapy was initiated, as is the protocol in this condition. Eighteen years after the diagnosis, the patient is clinically stable, fully autonomous and maintaining an acceptable quality of life, despite severe obstructive lung disease.

[Hepatopulmonary syndrome: case report and literature review]. / Síndroma hepatopulmonar: Relato de um caso clínico e revisão do tema.

Hepatopulmonary syndrome is an important complication of chronic liver disease occurring in 16 24% of patients. It is characterized by an increase in alveolar -capillary gradient, with or without hypoxemia, due to intrapulmonary vasodilatation. The course of the disease is progressive and associated with increased morbidity and mortality. There is no effective medical treatment and liver transplant is a priority. To exemplify the authors present the case of a 39 year -old male patient sent to the Pulmonology outpatient clinic and presenting with secondary polycythemia and progressive exertional dyspnoea. Clinical investigation identified a hepatopulmonary syndrome.