Protocol for a randomised, single-blind, two-arm, parallel-group controlled trial of the efficacy of rhinothermy delivered by nasal high flow therapy in the treatment of the common cold

Bird, Grace; Braithwaite, Irene; Harper, James; McKinstry, Steven; Koorevaar, Iris; Fingleton, James; Semprini, Alex; Dilcher, Meik; Jennings, Lance; Weatherall, Mark; Beasley, Richard

The common cold is the most common infectious disease affecting humans. [1] The common cold is a viral upper respiratory tract infection with typical symptoms that include: nasal congestion, rhinorrhoea, sneezing, sore throat, and cough. [2] Many viruses cause the common cold but Human Rhinoviruses (HRVs) are the most frequent pathogen. [3] On average, adults have two to four colds per year. [2] The mean duration of symptoms of the common cold is reported to be between seven and ten days and it is usually a self-limiting disease. [2] However, the common cold can cause significant morbidity and has a substantial economic impact on society. In the USA alone, non-influenza viral respiratory tract infections cause an estimated 20 million lost workdays, 110 million physician visits, and 6 million emergency department visits annually, [4] producing an economic burden of $40 billion each year. [4] Furthermore, HRV infection poses particular risks to those with other comorbidities such as asthma and chronic obstructive pulmonary disease (COPD), where they are a major cause of disease exacerbations. [5, 6] No effective treatment has been identified for the common cold and current treatments are mainly symptomatic. There are many cold remedies marketed and, for example, in the USA an estimated $2.9 billion are spent on over-the-counter medications for the common cold annually. [4] Amongst the treatment used are: zinc, vitamin C, nasal decongestants, non-steroidal anti-inflammatory drugs (NSAIDs), echinacea, antihistamines, antibiotics and heated, humidified air. The evidence for the effectiveness of many of these is inconclusive or, at most, demonstrates limited benefit for symptom reduction. [3] Rhinothermy HRVs cause up to two thirds of colds, and importantly for the hypothesis tested in this research, have temperature-dependent replication. [7] The antiviral effect of temperature on HRVs has been investigated in vitro. [8] [9] [10] [11] Replication of most HRV strains is optimal between 33 and 35°C, [7] which is the normal physiological temperature of the upper airways. [7] Studies report that raising the nasal mucosal temperature may inhibit viral replication [8] and this may be a treatment strategy to attenuate the severity and duration of common cold symptoms. Forstall and colleagues report that the greatest inhibition of HRV occurs when exposed to a temperature of 43°C for at least one hour [7] F o r p e e r r e v i e w o n l y and Conti and colleagues report that HRV replication is suppressed when exposed to a temperature of 45°C for 20 minutes. [9] Rhinothermy is the delivery of heated, humidified air to the upper airways via the nasal passages.