Chronic cough is defined in adults as a cough that lasts for ≥8 weeks. When it proves intractable to standard-of-care treatment, it can be referred to as refractory chronic cough (RCC). Chronic cough is now understood to be a condition of neural dysregulation. Chronic cough and RCC result in a serious, often unrecognized, disease burden, which forms the focus of the current review.The estimated global prevalence of chronic cough is 2–18%. Patients with chronic cough and RCC report many physical and psychological effects, which impair their quality of life. Chronic cough also has a significant economic burden for the patient and healthcare systems. RCC diagnosis and treatment are often delayed for many years as potential treatable triggers must be excluded first and a stepwise empirical therapeutic regimen is recommended.Evidence supporting most currently recommended treatments is limited. Many treatments do not address the underlying pathology, are used off-label, have limited efficacy and produce significant side-effects. There is therefore a significant unmet need for alternative therapies for RCC that target the underlying disease mechanisms. Early clinical data suggest that antagonists of the purinergic P2X3 receptor, an important mediator of RCC, are promising, though more evidence is needed.

Background: The first confirmed case of novel coronavirus (2019-nCoV) infection in the United States was reported from the state of Washington in January, 2020. By March, 2020, New York City had become the epicenter of the outbreak in the United States. Methods: We tracked all patients with confirmed coronavirus-19 (COVID-19) infection admitted to intensive care units (ICU) at Montefiore Medical Center (Bronx, NY). Data were obtained through manual review of electronic medical records. Patients had at least 30 days of follow-up. Results: Our first 300 ICU patients were admitted March 10 through April 11, 2020. The majority (60.7%) of patients were men. Acute respiratory distress syndrome (ARDS) was documented in 91.7% of patients; 91.3% required mechanical ventilation. Prone positioning was employed in 58% of patients and neuromuscular blockade in 47.8% of mechanically-ventilated patients. Neither intervention was associated with decreased mortality. Vasopressors were required in 77.7% of patients. Acute kidney injury (AKI) was present on admission in 40.7% of patients, and developed subsequently in 36.0%; 50.9% of patients with AKI received renal replacement therapy (RRT). Overall 30-day mortality rate was 52.3%, and 55.8% among patients receiving mechanical ventilation. In univariate analysis, higher mortality rate was associated with increasing age, male sex, hypertension, obesity, smoking, number of comorbidities, AKI on presentation, and need for vasopressor support. A representative multivariable model for 30-day mortality is also presented, containing patient age, gender, body mass index, and AKI at admission. As of May 11, 2020, 2 patients (0.7%) remained hospitalized. Conclusions: Mortality in critical illness associated with COVID-19 is high. The majority of patients develop ARDS requiring mechanical ventilation, vasopressor-dependent shock, and AKI. The variation in mortality rates reported to date likely reflects differences in the severity of illness of the evaluated populations.

Guaifenesin, a mucoactive drug, acts by loosening mucus in the airways and making coughs more productive. It is used for relief of wet cough and chest congestion due to the common cold, and remains the only legally marketed expectorant in the US (per OTC Monograph). An ingredient in numerous over-the-counter (OTC) cough/cold medications, guaifenesin has a secondary indication for use in stable chronic bronchitis (professional indication). Clinical pharmacology and patient studies support the clinical utility of guaifenesin in respiratory conditions where mucus hypersecretion is prevalent: acute upper respiratory tract infections (URTIs), stable chronic bronchitis, and possibly rhinosinusitis. Guaifenesin has a well-established and favorable safety and tolerability profile in adult and pediatric populations. Its dosing range (200–400 mg 4-hourly, up to 6× daily) allows flexible dose titration to allow an increase of plasma concentrations. Multiple daily doses are needed to maintain 24-h therapeutic effect with immediate-release formulations. Extended-release guaifenesin tablet formulations are available, providing convenience with 12-hourly dosing and portability compared to liquids. Guaifenesin is considered as a safe and effective expectorant for the treatment of mucus-related symptoms in acute URTIs and stable chronic bronchitis. Its clinical efficacy has been demonstrated most widely in chronic respiratory conditions, where excess mucus production and cough are more stable symptoms. Progress is being made to establish clinical models and measures that are more appropriate for studying symptomatic relief with guaifenesin in acute respiratory infections. This will help generate the up-to-date and high-quality data needed to optimize guaifenesin’s effectiveness in established uses, and in new respiratory indications associated with mucus hypersecretion.