CHI3L1 is a susceptibility gene for asthma, bronchial hyperresponsiveness, and reduced lung function, and elevated circulating YKL-40 levels are a biomarker for asthma and decline in lung function.

Background Some Coronavirus disease 2019 (COVID-19) patients who have recovered from their acute infection after experiencing only mild symptoms continue to exhibit persistent exertional limitation that is often unexplained by conventional investigative studies. Research question What is the patho-physiological mechanism of exercise intolerance that underlies the post-COVID-19 long haul syndrome following COVID-19 in patients without cardio-pulmonary disease? Study Design and Methods This study examined the systemic and pulmonary hemodynamics, ventilation, and gas exchange in 10 post-COVID-19 patients without cardio-pulmonary disease during invasive cardiopulmonary exercise testing (iCPET) and compared the results to 10 age- and sex matched controls. These data were then used to define potential reasons for exertional limitation in the post-COVID-19 cohort. Results Post-COVID-19 patients exhibited markedly reduced peak exercise aerobic capacity (VO 2 ) compared to controls (70±11%predicted vs. 131±45%predicted; p<0.0001). This reduction in peak VO 2 was associated with impaired systemic oxygen extraction (i.e., narrow CaVO 2 /CaO 2 ) compared to controls (0.49±0.1 vs. 0.78±0.1, p<0.0001) despite a preserved peak cardiac index (7.8±3.1 vs. 8.4±2.3 L/min, p>0.05). Additionally, post-COVID-19 patients demonstrated greater ventilatory inefficiency (i.e., abnormal VE/VCO 2 slope: 35±5 vs. 27±5, p=0.01) compared to controls without an increase in dead space ventilation. Interpretation Post-COVID-19 patients without cardiopulmonary disease demonstrate a marked reduction in peak VO 2 from a peripheral rather than a central cardiac limit along with an exaggerated hyper-ventilatory response during exercise.

Streptococcus pneumoniae is an important global pathogen that causes a wide range of clinical disease in children and adults. Pneumococcal pneumonia is by far the common presentation of noninvasive and invasive pneumococcal disease and affects the young, the elderly, and the immunocompromised disproportionately. Patients with chronic pulmonary diseases are also at higher risk for pneumococcal infections. Substantial progress over the century has been made in the understanding of pneumococcal immunobiology and the prevention of invasive pneumococcal disease through vaccination. Currently, two pneumococcal vaccines are available for individuals at risk of pneumococcal disease: the 23-valent pneumococcal polysaccharide vaccine (PPV23) and the 13-valent pneumococcal protein-conjugate vaccine (PCV13). The goal of pneumococcal vaccination is to stimulate effective antipneumococcal antibody and mucosal immunity response and immunological memory. Vaccination of infants and young children with pneumococcal conjugate vaccine has led to significant decrease in nasal carriage rates and pneumococcal disease in all age groups. Recent pneumococcal vaccine indication and schedule recommendations on the basis of age and risk factors are outlined in this Focused Review. As new pneumococcal vaccine recommendations are being followed, continued efforts are needed to address the vaccine efficacy in the waning immunity of the ever-aging population, the implementation of vaccines using two different vaccines under very specific schedules and their real world clinical and cost effectiveness, and the development of next generation pneumococcal vaccines.

Rationale: Immune checkpoint inhibitors (ICIs) have revolutionized cancer care but are associated with unique adverse events, including potentially life-threatening pneumonitis. The diagnosis of ICI-pneumonitis is increasing; however, the biological mechanisms, clinical and radiologic features, and the diagnosis and management have not been well defined. Objectives: To summarize evidence, identify knowledge and research gaps, and prioritize topics and propose methods for future research on ICI-pneumonitis. Methods: A multidisciplinary group of international clinical researchers reviewed available data on ICI-pneumonitis to develop and refine research questions pertaining to ICI-pneumonitis. Results: This statement identifies gaps in knowledge and develops potential research questions to further expand knowledge regarding risk, biologic mechanisms, clinical and radiologic presentation, and management of ICI-pneumonitis. Conclusions: Gaps in knowledge of the basic biological mechanisms of ICI-pneumonitis, coupled with a precipitous increase in the use of ICIs alone or combined with other therapies, highlight the importance in triaging research priorities for ICI-pneumonitis.

Chronic myeloid leukemia (CML) is a myeloproliferative neoplasm, the incidence of which increases with age. Tyrosine kinase inhibitors (TKIs) are the mainstay of CML treatment, including imatinib, nilotinib, dasatinib, bosutinib, and ponatinib. Beyond matching patient disease profiles with TKI specificity, differences in the efficacy and toxicity profiles and a patient's comorbid risk factors should be considered when selecting the most appropriate agent. Our objectives are to review the incidence and severity of cardiovascular, metabolic, and pulmonary disorders associated with these TKIs, highlighting differences in adverse event profiles, suggested risk-mitigation strategies, and guidance for TKI selection in different settings. Patients receiving TKI agents for CML should be monitored for signs and symptoms of toxicity throughout therapy. Preemptive assessment, early toxicity recognition, and prompt management of cardiovascular, metabolic, and pulmonary toxicities can minimize treatment-limiting complications and improve outcomes in patients with CML.

The severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) pandemic poses extraordinary challenges. The tremendous number of coronavirus disease 2019 (COVID-19) cases in the United States has resulted in a large population of survivors with prolonged post-infectious symptoms. The creation of multidisciplinary post-COVID-19 clinics to address both persistent symptoms and potential long-term complications requires an understanding of the acute disease and the emerging data regarding COVID-19 outcomes. Experience with severe acute respiratory syndrome and Middle East respiratory syndrome, post-acute respiratory distress syndrome complications, and post-intensive care syndrome also informs anticipated sequelae and clinical program design. Post-COVID-19 clinical programs should be prepared to care for individuals previously hospitalized with COVID-19 (including those who required critical care support), non-hospitalized individuals with persistent respiratory symptoms following COVID-19 infection, and individuals with pre-existing lung disease complicated by COVID-19. Effective multidisciplinary collaboration models leverage lessons learned during the early phases of the pandemic to overcome the unique logistical challenges posed by pandemic circumstances. Collaboration between clinicians and researchers across disciplines will provide insight into survivorship that may shape the treatment of both acute disease and chronic complications. In this review, we discuss the aims, general principles, elements of design, and challenges of a successful multidisciplinary model to address the needs of COVID-19 survivors.

; on behalf of the RENEW Study Group * BACKGROUND: The Lung Volume Reduction Coil Treatment in Patients With Emphysema (RENEW) trial reported improvements in quality of life, pulmonary function, and exercise performance following endobronchial coil treatment. OBJECTIVES: The purpose of this post hoc analysis was to identify baseline predictors, including quantitative CT measures, that identify patients most likely to significantly benefit from endobronchial coil therapy. METHODS: Quantitative CT analysis by an independent radiology laboratory and a qualitative evaluation by five blinded experts of the baseline thoracic CT imaging were performed. Univariate and multivariate logistic regression analyses were performed to elucidate characteristics associated with clinical response. RESULTS: In total, 125 patients underwent coil treatment and had evaluable 12-month followup results. Of these, 78 patients received treatment of lobes with the highest emphysematous destruction determined by quantitative CT analysis (quantitative visual match [QVM]þ), and 47 received treatment in at least one lobe that was not the most destroyed (QVM-). From the 78 patients with QVMþ treatment, a subgroup of 50 patients (64%) was identified with baseline residual volume > 200% predicted, emphysema score > 20% low attenuation area, and absence of airway disease. In this subgroup, greater lobar residual volume reduction in the treated lobes was achieved, which was associated with significant mean AE SE improvement in FEV 1 (15.2 AE 3.1%), St. George's Respiratory Questionnaire (-12 AE 2 points), and residual volume (-0.57 AE 0.13 L). DISCUSSION: This post hoc analysis found that both significant hyperinflation (residual volume $ 200% predicted) and CT analysis are critical for patient selection and treatment planning for endobronchial coil therapy. Quantitative CT analysis is important to identify optimal lobar treatment and to exclude patients with insufficient emphysema (< 20% low attenuation area), whereas visual assessment identifies patients with signs of airway disease associated with worse outcomes.

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