Patients admitted to the ICU with critical COVID-19 often require prolonged periods of mechanical ventilation. Difficulty weaning, lack of progress, and clinical deterioration are commonly encountered. These conditions should prompt a thorough evaluation for persistent or untreated manifestations of COVID-19, as well as complications from COVID-19 and its various treatments. Inflammation may persist and lead to fibroproliferative changes in the lungs. Infectious complications may arise including bacterial superinfection in the earlier stages of disease. Use of immunosuppressants may lead to the dissemination of latent infections, and to opportunistic infections. Venous thromboembolic disease is common, as are certain neurologic manifestations of COVID-19 including delirium and stroke. High levels of ventilatory support may lead to ventilator-induced injury to the lungs and diaphragm. We present diagnostic and therapeutic considerations for the mechanically ventilated patient with COVID-19 who shows persistent or worsening signs of critical illness, and we offer an approach to treating this complex but common scenario.

Multiparametric risk assessment is used in pulmonary arterial hypertension (PAH) to target therapy. However, this strategy is imperfect because most patients remain at intermediate or high risk after initial treatment, with low risk being the goal. Metrics of right ventricular (RV) adaptation are promising tools that may help refine our therapeutic strategy.

Nontuberculous mycobacterial pulmonary disease (NTM-PD) continues to impose a significant clinical burden of disease on susceptible patients. The incidence of NTM-PD is rising globally, but it remains a condition that is challenging to diagnose and treat effectively. This review provides an update on the global epidemiologic features, risk factors, and diagnostic considerations associated with the management of NTM-PD.

Direct oral anticoagulants (DOACs) are an alternative to low-molecular-weight heparin for treating cancer-associated VTE.

Asthma-COPD overlap (ACO) is a heterogeneous condition that describes patients who show persistent airflow limitation with clinical features that support both asthma and COPD. Although no single consensus definition exists to diagnose this entity, common major criteria include a strong bronchodilator reversibility or bronchial hyperreactivity, a physician diagnosis of asthma, and a ≥ 10-pack-year cigarette smoking history. The prevalence of ACO ranges from 0.9% to 11.1% in the general population, depending on the diagnostic definition used. Notably, patients with ACO experience greater symptom burden, worse quality of life, and more frequent and severe respiratory exacerbations than those with asthma or COPD. The underlying pathophysiologic features of ACO have been debated. Although emerging evidence supports the role of environmental and inhalational exposures in its pathogenesis among patients with a pre-existing airway disease, biomarker profiling and genetic analyses suggest that ACO may be a heterogeneous condition, but with definable characteristics. Early-life factors including childhood-onset asthma and cigarette smoking may interact to increase the risk of airflow obstruction later in life. For treatment options, the population with ACO historically has been excluded from therapeutic trials; therefore strong, evidence-based recommendations are lacking beyond first-line inhaler therapies. Advanced therapies in patients with ACO are selected according to disease phenotypes and are based on extrapolated data from asthma and COPD. Research focused on defining biomarkers and evidence-based treatment options for ACO is needed urgently.

A 51-year-old White male never-smoker presented with intermittent cough and progressive dyspnea. His symptoms started after an exposure to bat guano while cleaning his attic approximately 9 months earlier. He has received several courses of antibiotic and corticosteroid for these symptoms, with short-term relief.

A 58-year-old woman presented to a pulmonology clinic for evaluation of bilateral pulmonary nodules. Two years previously, she had presented with atrioventricular nodal reentrant tachycardia. During evaluation for her tachyarrhythmia, transthoracic echocardiogram (TTE) revealed a large, homogenous, highly mobile right atrial and ventricular mass. She underwent electrophysiologic ablation, tricuspid valve annular ring replacement, and resection of the mass, which pathology confirmed to be a myxoma. Now, a recent abdomen and pelvis CT study obtained for history of nephrolithiasis incidentally noted bilateral lower lobe pulmonary nodules. Follow-up noncontrast chest CT confirmed bilateral peribronchovascular solid pulmonary nodules up to 8 mm in diameter throughout all lobes. The nodules appeared contiguous with the segmental and subsegmental bronchovascular bundles, and many occurred at branch points. There was no mediastinal or hilar lymphadenopathy. To evaluate the pulmonary nodules, she was referred to a pulmonology clinic. She reported only stable, nonlimiting dyspnea on exertion. She did not have a cough. She denied a history of fevers, weight loss, or night sweats. She had no rash or skin changes, visual changes, joint pain or swelling, or palpitations. She had no history of oropharyngeal or genital ulcerations. Social history was notable for a 40-pack-year smoking history, with quit date 2 years prior. She had no risk factors for TB exposure and no exposures to sandblasting, stone cutting, or other environmental risk factors for silicosis. Family history was negative for autoimmune conditions, sarcoidosis, and lymphoproliferative disorders.

A 70-year-old man was referred for evaluation of recurrent respiratory infections requiring antibiotics and chronic cough over 3 years. Two months prior to presentation, he started to develop blood-tinged sputum but not frank hemoptysis. He otherwise denied any fever, chills, night sweats, or weight loss. He had dyspnea during the respiratory infections but not otherwise. His medical history was significant for chronic rhinitis without sinusitis and a low serum IgM level. He was a never smoker and a farmer but otherwise had no significant or specific exposures or travel history. His family history was significant for alpha-1 antitrypsin deficiency in his mother.

A 30-year-old woman was referred with increasing shortness of breath and cough in the setting of GATA2 deficiency. She initially presented 9 years previously with recurrent episodes of pneumonia and sinusitis. Genetic testing revealed a heterozygous GATA2 mutation (c.988C>T). She has since had multiple infections that have included necrotizing fasciitis of the right thumb, recurrent pilonidal infections (which required 23 procedures), esophageal candidiasis, and human papillomavirus-positive high-grade squamous intraepithelial lesion of the cervix. Serial bone marrow biopsy specimens showed persistent hypocellularity (20% to 60%) with intermittent erythroid atypia and variable detection of trisomy 8, which were concerning for evolving myelodysplastic syndrome. One year before the current admission, she was diagnosed with disseminated Mycobacterium avium complex and was treated with rifabutin, ethambutol, and azithromycin. She was taking voriconazole, acyclovir, and trimethoprim-sulfamethoxazole prophylaxis.

A 30-year-old transgender woman who was HIV positive presented to the ED with progressive severe dyspnea and hemoptysis that started 1 day earlier. The patient was undergoing antiretroviral therapy with emtricitabine-rilpivirine-tenofovir with good compliance and feminizing hormone therapy with cyproterone acetate. She was otherwise healthy and was not taking any other medications.

Excessive dynamic airway collapse (EDAC) contributes to breathlessness and reduced quality of life in individuals with emphysema. We tested a novel, portable, oral positive expiratory pressure (o-PEP) device in a patient with emphysema and EDAC. MRI revealed expiratory tracheal narrowing to 80 mm2 that increased to 170 mm2 with the o-PEP device. After 2-weeks use of the o-PEP device for 33% to 66% of activities, breathlessness, quality of life, and exertional dyspnea improved compared with minimal clinically important differences (MCID): University of California-San Diego Shortness of Breath questionnaire score declined 69 to 42 (MCID, ≥5), St. George's Respiratory Questionnaire score decreased 71 to 27 (MCID, ≥4), and before and after the 6-minute walk test Borg score difference improved from Δ3 to Δ2 (MCID, ≥1). During the 6-minute walk test on room air without the use of the o-PEP device, oxyhemoglobin saturation declined 91% to 83%; whereas, with the o-PEP device, the nadir was 90%. Use of the o-PEP device reduced expiratory central airway collapse and improved dyspnea, quality of life, and exertional desaturation in a patient with EDAC and emphysema.