Daily Respiratory Research Analysis

In a double-blind RCT of 99 adults with refractory chronic cough, flupentixol–melitracen for 2 weeks nearly doubled the clinically meaningful cough resolution rate versus placebo (65.3% vs 32.0%) and produced greater reductions in symptom scores, without serious adverse events. All adverse events were mild and resolved on discontinuation. Short duration and lack of objective cough monitoring warrant confirmation in larger, multi-center studies.

Impact: This is a rigorously designed randomized trial demonstrating a clinically meaningful benefit in a difficult-to-treat population with limited options. It provides an immediately testable therapeutic avenue and may reshape management algorithms for refractory chronic cough.

Clinical Implications: Consider flupentixol–melitracen as an adjunct for refractory chronic cough unresponsive to neuromodulators, with monitoring for tolerability. Clinicians should be aware evidence is short-term and symptom-based; objective cough monitoring and longer-term safety remain to be defined.

Future Directions: Multi-center RCTs with objective cough monitors and longer follow-up to assess durability, quality-of-life, and relapse; exploration of responder phenotypes and pharmacovigilance for neuropsychiatric effects.

Across three coronaviruses and epithelial systems, infection increased ceramide and decreased sphingomyelin, implicating neutral sphingomyelinase 2 (nSMase2)–driven sphingomyelin-to-ceramide conversion. Pharmacologic and genetic inhibition of nSMase2 reduced replication and prevented formation of double-membrane replication organelles, with ceramide and nSMase2 colocalizing to these structures. The work identifies a conserved, druggable host lipid pathway essential for coronavirus replication.

Impact: Revealing a conserved host lipid enzyme required for replication organelle biogenesis advances a paradigm for host-targeted, broad-spectrum antivirals against coronaviruses, complementing spike- or polymerase-directed strategies.

Clinical Implications: Although preclinical, nSMase2 and ceramide remodeling provide a tractable host pathway for antiviral development that may retain efficacy across variants and coronaviruses. Safety profiling of sphingolipid-modulating agents and in vivo validation are next steps.

Future Directions: Validate nSMase2 dependence in vivo; assess antiviral efficacy and safety of nSMase2 inhibitors; map downstream ceramide species and membrane biophysics governing organelle biogenesis; explore combinatorial strategies with direct-acting antivirals.

Using matched cohorts from a >118-million patient EHR network, COVID-19 infection increased 3-month risk of incident asthma (HR 1.656), allergic rhinitis (HR 1.272), and chronic rhinosinusitis (HR 1.744), while atopic dermatitis and eosinophilic esophagitis were unchanged. Vaccination was associated with reduced risks of asthma (HR 0.678) and chronic rhinosinusitis (HR 0.799), indicating a 2–3-fold safer respiratory type 2 inflammatory profile compared with infection.

Impact: This large-scale, propensity-matched analysis quantifies post-COVID respiratory type 2 inflammatory risks and shows vaccination’s protective association, informing clinical surveillance and public health messaging.

Clinical Implications: Counsel patients that COVID-19 infection elevates short-term risks of asthma and chronic rhinosinusitis; vaccination is associated with lower risks. Consider proactive monitoring and early management for respiratory type 2 conditions after infection, especially in at-risk individuals.

Future Directions: Extend follow-up to define long-term incidence and remission; stratify by variants, vaccination schedules, and baseline atopy; mechanistic studies to link viral triggers to type 2 airway inflammation.