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Many patients with obstructive sleep apnea syndrome (OSAS), despite therapy with nasal continuous positive airway pressure (CPAP), have persisting daytime somnolence that may be due to a persistently elevated upper-airway resistance associated with electroencephalographic (EEG) arousals. We tested the hypothesis that elevated upper-airway resistance can be inferred from the contour of the inspiratory flow tracing obtained from a conventional CPAP circuit. This may provide a noninvasive method for determining optimal CPAP. Data were collected during a CPAP titration of an upper-airway model and in eight patients with OSAS. Estimated inspiratory resistance was calculated from esophageal pressure, CPAP mask pressure, and inspiratory flow. At high CPAP, resistance was low and inspiratory flow contour was found to be rounded. At low CPAP, resistance was high and flow contour developed a plateau suggesting flow limitation. We also noted that the CPAP pressure at which high resistance developed, and at which flow limitation appeared, showed hysteresis. We conclude that when respiration is stable, the contour of inspiratory flow tracing from a CPAP system can be used to infer the presence of elevated upper-airway resistance and flow limitation. Optimizing flow contour may be an alternative to eliminating apneas in evaluation of the optimal therapeutic level of CPAP in OSAS.

We investigated the in vivo effect of coinfection of Mycobacterium tuberculosis on human immunodeficiency virus type 1 (HIV-1) replication using bronchoalveolar lavage (BAL) of 11 HIV-1-infected patients with pulmonary tuberculosis and 10 patients with no lung disease. Lung segments involved with pulmonary tuberculosis had significantly elevated HIV-1 branched DNA (bDNA) levels and p24 in BAL compared with lung segments uninvolved with tuberculosis or with BAL from patients with no lung disease. The BAL viral burden was higher than plasma HIV-1 in tuberculosis patients, indicating local production of virus. BAL HIV-1 bDNA declined over the course of treatment for tuberculosis in three patients who underwent serial bronchoscopies. Tumor necrosis factor-alpha (TNF-alpha) and HIV-1 bDNA particles were strongly correlated (r2 = 0.9, p < 0.01) in lung segments involved with tuberculosis. The deduced amino acid sequence of HIV-1 gp120 V3 region from involved segments of three patients with pulmonary tuberculosis showed basic substitutions associated with altered viral phenotype. Phylogenetic analysis of V3 sequences demonstrated that BAL HIV-1 RNA had diverged from plasma. These data support the conclusion that pulmonary tuberculosis enhances local HIV-1 replication in vivo.

The acute course of coronavirus disease 2019 (COVID-19) is variable and ranges from asymptomatic infection to fulminant respiratory failure. Patients recovering from COVID-19 can have persistent symptoms and computed tomography (CT) abnormalities of variable severity. At 3 months after acute infection, a subset of patients will have CT abnormalities that include ground glass abnormalities (GGO) and subpleural bands with concomitant pulmonary function abnormalities. At 6 months after acute infection, some patients have persistent CT changes to include the resolution of GGOs seen in the early recovery phase and the persistence or development of changes suggestive of fibrosis such as reticulation with or without parenchymal distortion. Predictors of post-COVID lung disease include need for intensive care unit (ICU) admission, mechanical ventilation, higher inflammatory markers, longer hospital stay and a diagnosis of acute respiratory distress syndrome (ARDS). Treatments of post-COVID lung disease are being investigated with anti-fibrotic agents being investigated for the prevention of post-COVID lung fibrosis. The etiology of post-COVID lung disease may be a sequela of prolonged mechanical ventilation, COVID-induced ARDS or direct injury from the virus. Future research is needed to determine the long-term persistence of post-COVID lung disease, its impact on patients and ways to prevent or treat it.

Local cellular immune responses may affect presentation and outcome in tuberculosis (TB). To investigate this hypothesis, we performed bronchoalveolar lavage (BAL) on 30 patients with untreated pulmonary tuberculosis and assessed the type of cellular inflammatory response and cytokine production. We then correlated BAL findings and cytokine production with clinical findings. We also performed BAL on a subset of patients to examine changes in cytokine production by BAL cells over time. We found that at presentation patients with less clinically and radiographically advanced TB (smear-negative, noncavitary disease) had a local immune response characterized by a predominance of lymphocytes. Furthermore, BAL cells from these patients secreted interferon (IFNgamma), and not Interleukin-4, suggesting a Th 1-type lymphocytic response. In patients with smear-positive and/or cavitary disease, macrophages or polymorphonuclear leukocytes were the predominant BAL cell type, but with treatment and clinical improvement these patients went on to recruit IFNgamma producing cells to the lung. We conclude that the type of cellular immune response that occurs locally in the lung may affect presentation and outcome in pulmonary TB, and an understanding of the development of this response may lead to insights into pathogenesis and novel therapies for TB.

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BackgroundCurrent treatment regimens for pulmonary tuberculosis require at least 6 months of therapy. Immune adjuvant therapy with recombinant interferon-γ1b (rIFN-γb) may reduce pulmonary inflammation and reduce the period of infectivity by promoting earlier sputum clearance.Methodology/Principal FindingsWe performed a randomized, controlled clinical trial of directly observed therapy (DOTS) versus DOTS supplemented with nebulized or subcutaneously administered rIFN-γ1b over 4 months to 89 patients with cavitary pulmonary tuberculosis. Bronchoalveolar lavage (BAL) and blood were sampled at 0 and 4 months. There was a significant decline in levels of inflammatory cytokines IL-1β, IL-6, IL-8, and IL-10 in 24-hour BAL supernatants only in the nebulized rIFN-γ1b group from baseline to week 16. Both rIFN-γ1b groups showed significant 3-fold increases in CD4+ lymphocyte response to PPD at 4 weeks. There was a significant (p = 0.03) difference in the rate of clearance of Mtb from the sputum smear at 4 weeks for the nebulized rIFN-γ1b adjuvant group compared to DOTS or DOTS with subcutaneous rIFN-γ1b. In addition, there was significant reduction in the prevalence of fever, wheeze, and night sweats at 4 weeks among patients receiving rFN-γ1b versus DOTS alone.ConclusionRecombinant interferon-γ1b adjuvant therapy plus DOTS in cavitary pulmonary tuberculosis can reduce inflammatory cytokines at the site of disease, improve clearance of Mtb from the sputum, and improve constitutional symptoms.Trial RegistrationClinicalTrials.gov NCT00201123