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The lung microbiome impacts on lung function, making any smoking-induced changes in the lung microbiome potentially significant. The complex co-occurrence and co-avoidance patterns between the bacterial taxa in the lower respiratory tract (LRT) microbiome were explored for a cohort of active (AS), former (FS) and never (NS) smokers. Bronchoalveolar lavages (BALs) were collected from 55 volunteer subjects (9 NS, 24 FS and 22 AS). The LRT microbiome composition was assessed using 16S rRNA amplicon sequencing. Identification of differentially abundant taxa and co-occurrence patterns, discriminant analysis and biomarker inferences were performed. The data show that smoking results in a loss in the diversity of the LRT microbiome, change in the co-occurrence patterns and a weakening of the tight community structure present in healthy microbiomes. The increased abundance of the genus Ralstonia in the lung microbiomes of both former and active smokers is significant. Partial least square discriminant and DESeq2 analyses suggested a compositional difference between the cohorts in the LRT microbiome. The groups were sufficiently distinct from each other to suggest that cessation of smoking may not be sufficient for the lung microbiota to return to a similar composition to that of NS. The linear discriminant analysis effect size (LEfSe) analyses identified several bacterial taxa as potential biomarkers of smoking status. Network-based clustering analysis highlighted different co-occurring and co-avoiding microbial taxa in the three groups. The analysis found a cluster of bacterial taxa that co-occur in smokers and non-smokers alike. The clusters exhibited tighter and more significant associations in NS compared to FS and AS. Higher degree of rivalry between clusters was observed in the AS. The groups were sufficiently distinct from each other to suggest that cessation of smoking may not be sufficient for the lung microbiota to return to a similar composition to that of NS.

A 64-year-old man experienced persistent atelectasis of the right lung after right upper lobectomy. To simultaneously visualize the airways and lung parenchyma in real time, chest computed tomography was performed while pneumatically splinting the lung open via insufflation through the working channel of a bronchoscope. The bronchi were patent but peripheral consolidations within the remaining right lung were visualized, representative of pneumonia. The patient fully recovered with antimicrobial therapy. Computed tomography during bronchoscopic pneumatic lung splinting is an advanced diagnostic for the investigation of persistent atelectasis.

Background: EBUS-TBNA is an integral tool in the diagnosis and staging of lung cancer and other diseases involving mediastinal lymphadenopathy. Most studies attesting to the performance of EBUS-TBNA are prospective analyses performed under strict protocols. The objective of our study was to compare the accuracy of EBUS-TBNA to surgery in diagnosing hilar and mediastinal pathologies in a tertiary hospital, staffed by pulmonologists with and without formal interventional pulmonary training. Methods: We retrospectively analyzed subjects who underwent EBUS-TBNA followed by a confirmatory surgical procedure from January 2012 to December 2018. The primary outcome was to evaluate the accuracy of EBUS-TBNA in the diagnosis of all mediastinal disease. Secondary analyses determined the accuracy of EBUS-TBNA in cancer, NSCLC, and non-malignant lesions individually. Results: One hundred and forty-three subjects had an EBUS-TBNA procedure followed by surgery. EBUS-TBNA for all pathologies had an accuracy of 81.2% (CI 95% 73.8-87.4) and sensitivity of 55.1% (CI 95% 41.5-68.3). The accuracy and sensitivity of individual groups were: cancer (81.7, 48.8%), NSCLC (84, 48.3%), and non-malignancy (78.9, 60%). The NSCLC group had 15 false negatives and 5 (33.3%) of them were due to non-sampling of EBUS accessible nodes. Missed sampling led to a change in the final staging in 8.6% of NSCLC subjects. Conclusion: The accuracy of EBUS-TBNA across all groups was comparable to those reported previously. However, the sensitivity was comparatively lower. This was primarily due to the large number of EBUS-TBNA accessible lymph nodes that were not sampled. This data highlights the need for guidelines outlining the best sampling approach and lymph node selection.

In patients with a history of cancer, mediastinal adenopathy often heralds a recurrence of their malignancy. However, not all mediastinal adenopathy is due to cancer recurrence. We report a series of patients with cancer and new mediastinal lymphadenopathy with granulomatous inflammation. Method: Retrospective review (2011-2015) of all 511 consecutive patients referred for EBUS-TBNA for mediastinal and/or hilar lymphadenopathy identified by CT and/or PET imaging. Patients with lung cancer were specifically excluded. Results: We identified 27 patients (5.2 %) with prior cancer history with non-caseating granulomas. 2 patients had a newly diagnosis of colon cancer. 2 had unexpected newly diagnosis of lung cancer. All others, 25 had prior diagnosis of cancer. A focused review with the help of cell block and CD68 immunostaining identified granulomas in 25% of the lymph nodes aspirates, originally not reported by pathologists.Two patients required mediastinoscopy. There was no evidence of mycobacterial infection. Follow up images revealed disappearance of lymphadenopathy in some patients and stability of findings in all others. Conclusion: EBUS-TBNA can detect granulomas but a cell block, CD68 immunostaining and a learning curve by general pathologists are strongly recommended. PET scan does not distinguish cancer recurrence versus granulomatous inflammation. Sarcoid-like lymphadenopathy may be reversible and have a good prognosis in patients with cancer.

Endoscopic ultrasound-guided fine-needle aspiration (EUS FNA) has a high accuracy in the evaluation of mediastinal lesions. The use of a core biopsy needle for EUS guided biopsy (EUS TCB) may further improve the yield of EUS. The aims of this study are to evaluate the safety of EUS TCB in thoracic lesions and to compare the diagnostic accuracy of TCB with FNA and FNA + TCB.A single-center retrospective study. All patients underwent EUS-FNA and TCB. A cytopathologist was not present during the procedure. EUS FNA, TCB and FNA + TCB diagnostic accuracy were compared.A total of 48 patients were included. The lesions sampled included 41 lymph nodes (six aorto-pulmonary window, 32 subcarinal, two right paratracheal, one paraesophageal ATS station 8), five lung masses, and two esophageal masses. Twenty-nine patients had malignant disease and 19 had benign disorders. The overall diagnostic accuracy of FNA, TCB and FNA + TCB was 79%, 79% and 98% respectively (p = 0.007). TCB changed the diagnosis in nine cases missed by FNA. EUS TCB was better than FNA for benign diseases (89% vs. 63%, p = 0.04). All eight patients with a prior failed biopsy had a correct diagnosis established by EUS. No patient required mediastinoscopy or thoracoscopy after EUS.The combination of TCB and FNA is superior to FNA alone. EUS-guided TCB should be considered in patients with benign disorders of the mediastinum when other modalities fail to yield a diagnosis.

We investigated whether the bronchodilator response to a beta-adrenergic agonist is influenced by the mechanism of induced bronchoconstriction. Normal subjects and asymptomatic asthmatics inhaled a dry aerosol (mass median aerodynamic diameter, 1.5 microns) with increasing concentrations of methacholine or histamine to produce a 35% decrease in specific airway conductance (SGaw), followed by a single inhalation of a metaproterenol aerosol. By studying normal subjects and asthmatics, we were able to compare metaproterenol responsiveness after widely divergent doses of the bronchoprovocative agents but the same degree of bronchoconstriction. Airway deposition of methacholine, histamine, and metaproterenol was measured using a quinine fluorescence technique. Mean baseline SGaw, metaproterenol responsiveness, and metaproterenol mass deposited were similar in normal subjects and asthmatics. Likewise, mean SGaw after completion of methacholine and histamine challenge, and the subsequently deposited metaproterenol mass were similar in the two groups. After methacholine challenge (mean +/- SD provocative drug mass causing a 35% decrease in SGaw, PM35: 8.94 +/- 5.96 mumol in normal subject and 0.30 +/- 0.29 mumol in asthmatics), metaproterenol increased mean SGaw by 89 +/- 33% in normal subjects and by 190 +/- 55% in asthmatics (p0.05, two-way analysis of variance). After histamine challenge (PM35, 2.92 +/- 2.49 mumol in normal subjects and 0.17 +/- 0.29 mumol in asthmatics), metaproterenol increased mean SGaw by 111 +/- 38% in normal subjects and 113 +/- 69% in asthmatics (p = not significant). Thus, for the same degree of bronchoconstriction, metaproterenol responsiveness was influenced by the dose of methacholine but not the dose of histamine. The differential metaproterenol response could be related to a functional antagonism between muscarinic and beta-adrenergic agonists.

7071 Background: Accurate staging is critical in defining which pts are surgical candidates in NSCLC. CT and 18FDG-PET can identify mediastinal lymphadenopathy (LAD) but lack specificity. Thoracoto...

This study explored the breathing patterns and arterial blood gases before and during cuprophane (CU) bicarbonate and polysulfone (PS) bicarbonate dialysis in six chronic dialysis patients with mild chronic obstructive pulmonary disease (COPD). The studies were performed in random order during two consecutive dialyses. Breathing patterns were monitored by respiratory impedance plethysmography. Apneic episodes, defined as a decrease in tidal volume of 75% lasting 10 sec, were present before and during hemodialysis. In these patients with COPD a high number of apneic episodes (17 +/- 6 [SE]) were observed during CU bicarbonate hemodialysis. Most of these episodes were central rather than obstructive in character. There were fewer events when the same patients were dialyzed with PS membranes (10 +/- 5; p = 0.05). The decrement in PO2 (baseline to 60 min) was 17 +/- 7 during CU and 4 +/- 5 mmHg during PS dialysis (p = 0.10). Minute ventilation decreased in four of six patients on CU bicarbonate and increased in all six patients on PS bicarbonate. It was concluded that bicarbonate hemodialysis does not completely prevent hypoxemia or apnea during dialysis in patients with COPD. Apneic episodes and hypoxemia appear to be less severe during PS bicarbonate than during CU bicarbonate hemodialysis.

INTRODUCTION: Idhiopatic thrombocytopenic purpura (ITP) is an autoimmune disease characterized by a premature destruction of platelets by macrophage, especially in the spleen. However in some cases, platelet sequestration and destruction may occur in other organs. Chromium labeled platelet sequestration study revealed that liver or precordial area are prominent sites of sequestration in some cases, suggesting that the lung might be the site in certain cases. Some cases of interstitial pneumonia are associated with immunologic injury to the lung and seen in patients with some autoimmune diseases, infections, drugs and transfusion related acute lung injury (TRALI) in which transfusions of platelets and blood products induce acute lung injury due to sequestration of platelets and neutrophils in lungs, sometimes leading to ARDS. We describe here an unusual association between ITP and interstitial pneumonia, suggesting that a lung injury similar to TRALI is involved in acute and recurrent ITP. METHODS: We have identified patients with ITP who developed interstitial pneumonia during the course of ITP. We reviewed their charts and analyzed their clinical courses of ITP and interstitial lung diseases. Laboratory tests and chest X ray or CAT scans were reviewed. The laboratory study included CBC, platelets and platelets activation was measured by PMP (platelet microparticles), expression of CD62p flowcytometrically. RESULTS: We have identified 6 patients with ITP who developed interstitial pneumonia during the course of ITP. In two of six, interstitial pneumonia was detected at the presentation of acute ITP. ITP was severe with platelet counts less than 10.000. Interstitial pneumonia was discovered incidentally by chest X ray and confirmed by CAT scans. A mild symptom of dyspnea was detected in careful examination. One underwent lung biopsy which showed findings consistent with brochiolitis obliterans organizing pneumonia. Repeated CAT scans in 1–3 months revealed marked improvement but residual interstitial infiltrates still persisted. Four others had a long standing chronic ITP with clinical courses characterized by frequent relapses in spite of surgical and medical therapy. Four of six patients had splenectomy. Interstitial lung diseases were detected at the time of a severe relapse with platelet counts of less than 20.000. One patient underwent chromium labeled platelet sequestration study which revealed rapid sequestration of platelets in the lung. Interstitial infiltrates improved following improvement of ITP but two progressed to interstitial pulmonary fibrosis. CD62P measured by flowcytometry was very high in all 3 patients tested, indicating persisting platelet activation in this clinical setting. SUMMARY: We report interstitial pneumonia developing in 6 patients with ITP. Clinically all were asymptomatic and detection of interstitial pneumonia was incidental radiology finding. A mild symptom of exertional dyspnea was present in careful investigation. Chest X ray or CT scans showed nonspecific interstitial infiltrates and showed an overall improvement within months but residual infiltrates persisted. Two progressed to pulmonary fibrosis. We suggest that platelets are sequestered and destroyed in the lung in some patients with ITP, to generate cytokines and lipid mediators that lead to a nonspecific interstitial lung disease.

The purpose of this study was to determine if the intersubject variability in airway responsiveness to methacholine is a function of the methacholine mass deposited in the airways and if methacholine hyperresponsiveness in asymptomatic subjects with asthma is related to increased methacholine deposition. Ten normal and 10 age-matched asymptomatic subjects with asthma inhaled, with a standardized single breath maneuver, a dry aerosol (mass median aerodynamic diameter, 1.5 micron; geometric SD, 2.1) generated from solutions of methacholine at concentrations ranging from 0.078 mg/ml to 80 mg/ml in buffered saline, mixed with a fixed concentration of the fluorescent tracer quinine. The mass of methacholine deposited was calculated from the fluorescence of the inspired and expired aerosol trapped on an absolute filter before inspiration and during expiration. Specific airway conductance (SGaw) was measured before and after the inhalation of increasing concentration of methacholine, and the provocative deposited mass corresponding to a 35% decrease in SGaw was calculated. Baseline aerosol deposition (quinine-labeled buffered saline) ranged from 63% to 94% and was similar in normal subjects (mean 85%) and asymptomatic subjects with asthma (mean 84%). There was a correlation between the decrease in SGaw and methacholine mass deposited at first dose in the normal subjects (p less than 0.001) but not in asymptomatic subjects with asthma. Mean provocative methacholine mass corresponding to a 35% decrease in SGaw was 86 micrograms (range 2 to 157 micrograms) in asymptomatic subjects with asthma and 1361 micrograms (range 157 to 3434 micrograms) in normal subjects (p less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

• A 52-year-old man with myxedema was evaluated for anterior chest pain that was considered to be compatible with myocardial ischemia. The night after admission he developed extreme bradycardia, hypotension, and apneic episodes lasting up to 25 s. Continuous positive airway pressure and administration of medroxyprogesterone acetate prevented further episodes and relieved much of the somnolence and lethargy that had contributed to the evidence for myxedema. Alveolar hypoventilation caused by decreased sensitivity to carbon dioxide, inadequate central neural drive, peripheral muscle force, and obesity all may have contributed to the apnea. Chest pain has not recurred, and results of electrocardiography have remained normal following full thyroid hormone replacement. The early recognition of myxedema causing sleep apnea will allow specific treatment to avoid the cardiovascular risks related to prolonged apnea and will help avoid confusion with other etiologies of cardiovascular abnormalities. (Arch Intern Med1987;147:1497-1499)