Dual-histamine receptor blockade with cetirizine - famotidine reduces pulmonary symptoms in COVID-19 patients.

BACKGROUND: The COVID-19 pandemic due to SARS-CoV-2 infection can produce Acute Respiratory Distress Syndrome as a result of a pulmonary cytokine storm. Antihistamines are safe and effective treatments for reducing inflammation and cytokine release. Combinations of Histamine-1 and Histamine-2 receptor antagonists have been effective in urticaria, and might reduce the histamine-mediated pulmonary cytokine storm in COVID-19. Can a combination of Histamine-1 and Histamine-2 receptor blockers improve COVID-19 inpatient outcomes? METHODS: A physician-sponsored cohort study of cetirizine and famotidine was performed in hospitalized patients with severe to critical pulmonary symptoms. Pulmonologists led the inpatient care in a single medical center of 110 high-acuity patients that were treated with cetirizine 10 mg b.i.d. and famotidine 20 mg b.i.d. plus standard-of-care. RESULTS: Of all patients, including those with Do Not Resuscitate directives, receiving the dual-histamine receptor blockade for at least 48 h, the combination drug treatment resulted in a 16.4% rate of intubation, a 7.3% rate of intubation after a minimum of 48 h of treatment, a 15.5% rate of inpatient mortality, and 11.0 days duration of hospitalization. The drug combination exhibited beneficial reductions in inpatient mortality and symptom progression when compared to published reports of COVID-19 inpatients. Concomitant medications were assessed and hydroxychloroquine was correlated with worse outcomes. CONCLUSIONS: This physician-sponsored cohort study of cetirizine and famotidine provides proof-of-concept of a safe and effective method to reduce the progression in symptom severity, presumably by minimizing the histamine-mediated cytokine storm. Further clinical studies in COVID-19 are warranted of the repurposed off-label combination of two historically-safe histamine receptor blockers.

The nose and sleep-disordered breathing: what we know and what we do not know.

The relationship between sleep-disordered breathing (SDB) and nasal obstruction is unclear. In order to better understand, we performed an extensive computer-assisted review and analysis of the medical literature on this topic. Data were grouped into reports of normal control subjects, patients with isolated nasal obstruction, and those with SDB. We conclude that SDB can both result from and be worsened by nasal obstruction. Nasal breathing increases ventilatory drive and nasal occlusion decreases pharyngeal patency in normal subjects. Nasal congestion from any cause predisposes to SDB. Although increased nasal resistance does not always correlate with symptoms of congestion, nasal congestion typically results in a switch to oronasal breathing that compromises the airway. Moreover, oral breathing in children may lead to the development of facial structural abnormalities associated with SDB. We postulate that the switch to oronasal breathing that occurs with chronic nasal conditions is a final common pathway for SDB.