The impact of cineole treatment timing on common cold duration and symptoms: Non-randomized exploratory clinical trial.

INTRODUCTION: Common cold (CC) symptoms arise from an inflammatory response treatable with cineole and generally peak within two days, which complicates research implementation. We therefore explored the benefits of early cineole administration with enrolment of participants prior to CC onset. METHODS: Out of 522 adults enrolled in our phase IV, open-label, non-randomized, exploratory clinical trial (EudraCT No. 2020-000860-51), 329 developed a CC and used 200 mg cineole (Soledum®, CNL-1976) t.i.d. for max. 15 (± 2) days. Primary endpoint was burden of disease based on the Wisconsin Upper Respiratory Symptom Survey (WURSS-11). RESULTS: Comparing three strata based on time to treatment (≤ 12 h, > 12 to ≤ 24 h and > 24 h), earliest treatment resulted in lowest AUC-WURSS (Spearman correlation coefficient of 0.36) and reduced the overall burden of disease by 38% (p < 0.0001). Earlier and lower symptom severity peak resulted, with shorter time to remission (average 8.9 vs. 10.7 days with latest treatment initiation, p < 0.05), and higher and faster recovering quality of life (p < 0.05). Tolerability was mostly rated as "very good", with adverse events of suspected causal relationship reported in 4.3% of participants. CONCLUSIONS: Early intervention shows clinical benefits relevant for the effective treatment of CC with cineole.

Low early life socioeconomic status and susceptibility to the common cold in adulthood: The moderating role of negative affective reactivity.

OBJECTIVE: Socioeconomic disadvantage during childhood and adolescence is associated with higher risk for many physical health problems, including infectious disease, throughout the lifespan. Greater negative affective (NA) reactivity has shown similar links to greater risk for physical health conditions and altered patterns of biological functioning associated with acute respiratory infection as socioeconomic disadvantage; yet their interactive effects on physical health outcomes have not been examined. Thus, the present study examined whether NA reactivity accentuated the link between early socioeconomic disadvantage and susceptibility to the common cold. METHOD: Participants were 212 adults (42% female, 18-55 years old) who completed measures of childhood socioeconomic status (SES; parental home ownership) and were subsequently exposed to a virus that causes the common cold. Participants then remained quarantined for 5 days, during which multiple indicators of viral infection and clinical illness were assessed. Before and after quarantine, participants completed a laboratory stress task to assess NA reactivity. RESULTS: NA reactivity moderated the relationship between parental home ownership and clinical cold diagnosis in adulthood (b = -0.11, p = .018), such that fewer years of parental home ownership was associated with increased odds for developing a cold only among adults who had greater NA reactivity (OR = 0.89, 95% confidence interval, CI [0.82, 0.96]), but not among those who had lower NA reactivity (OR = 1.01, 95% CI [0.94, 1.09]). CONCLUSIONS: These findings suggest that how individuals negatively react to psychosocial stressors in adulthood may exacerbate the impact of childhood SES on acute infection susceptibility. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Immediate versus delayed versus no antibiotics for respiratory infections.

BACKGROUND: Concerns exist regarding antibiotic prescribing for respiratory tract infections (RTIs) owing to adverse reactions, cost and antibacterial resistance. One proposed strategy to reduce antibiotic prescribing is to provide prescriptions, but to advise delay in antibiotic use with the expectation that symptoms will resolve first. This is an update of a Cochrane Review originally published in 2007, and updated in 2010, 2013 and 2017. OBJECTIVES: To evaluate the effects on duration and/or severity of clinical outcomes (pain, malaise, fever, cough and rhinorrhoea), antibiotic use, antibiotic resistance and patient satisfaction of advising a delayed prescription of antibiotics in respiratory tract infections. SEARCH METHODS: From May 2017 until 20 August 2022, this was a living systematic review with monthly searches of the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase, CINAHL and Web of Science. We also searched the WHO International Clinical Trials Registry Platform (ICTRP) and ClinicalTrials.gov on 20 August 2022. Due to the abundance of evidence supporting the review's key findings, it ceased being a living systematic review on 21 August 2022. SELECTION CRITERIA: Randomised controlled trials involving participants of all ages with an RTI, where delayed antibiotics were compared to immediate or no antibiotics. We defined a delayed antibiotic as advice to delay the filling of an antibiotic prescription by at least 48 hours. We considered all RTIs regardless of whether antibiotics were recommended or not. DATA COLLECTION AND ANALYSIS: We used standard Cochrane methodological procedures. MAIN RESULTS: For this 2022 update, we added one new trial enrolling 448 children (436 analysed) with uncomplicated acute RTIs. Overall, this review includes 12 studies with a total of 3968 participants, of which data from 3750 are available for analysis. These 12 studies involved acute RTIs including acute otitis media (three studies), streptococcal pharyngitis (three studies), cough (two studies), sore throat (one study), common cold (one study) and a variety of RTIs (two studies). Six studies involved only children, two only adults and four included both adults and children. Six studies were conducted in primary care, four in paediatric clinics and two in emergency departments. Studies were well reported and appeared to provide moderate-certainty evidence. Randomisation was not adequately described in two trials. Four trials blinded the outcome assessor, and three included blinding of participants and doctors. We conducted meta-analyses for pain, malaise, fever, adverse effects, antibiotic use and patient satisfaction. Cough (four studies): we found no differences amongst delayed, immediate and no prescribed antibiotics for clinical outcomes in any of the four studies. Sore throat (six studies): for the outcome of fever with sore throat, four of the six studies favoured immediate antibiotics, and two found no difference. For the outcome of pain related to sore throat, two studies favoured immediate antibiotics, and four found no difference. Two studies compared delayed antibiotics with no antibiotic for sore throat, and found no difference in clinical outcomes. Acute otitis media (four studies): two studies compared immediate with delayed antibiotics - one found no difference for fever, and the other favoured immediate antibiotics for pain and malaise severity on Day 3. Two studies compared delayed with no antibiotics: one found no difference for pain and fever severity on Day 3, and the other found no difference for the number of children with fever on Day 3. Common cold (two studies): neither study found differences for clinical outcomes between delayed and immediate antibiotic groups. One study found delayed antibiotics were probably favoured over no antibiotics for pain, fever and cough duration (moderate-certainty evidence). ADVERSE EFFECTS: there were either no differences for adverse effects or results may have favoured delayed over immediate antibiotics with no significant differences in complication rates (low-certainty evidence). Antibiotic use: delayed antibiotics probably resulted in a reduction in antibiotic use compared to immediate antibiotics (odds ratio (OR) 0.03, 95% confidence interval (CI) 0.01 to 0.07; 8 studies, 2257 participants; moderate-certainty evidence). However, a delayed antibiotic was probably more likely to result in reported antibiotic use than no antibiotics (OR 2.52, 95% CI 1.69 to 3.75; 5 studies, 1529 participants; moderate-certainty evidence). Patient satisfaction: patient satisfaction probably favoured delayed over no antibiotics (OR 1.45, 1.08 to 1.96; 5 studies, 1523 participants; moderate-certainty evidence). There was probably no difference in patient satisfaction between delayed and immediate antibiotics (OR 0.77, 95% CI 0.45 to 1.29; 7 studies, 1927 participants; moderate-certainty evidence). No studies evaluated antibiotic resistance. Reconsultation rates and use of alternative medicines were similar for delayed, immediate and no antibiotic strategies. In one of the four studies reporting use of alternative medicines, less paracetamol was used in the immediate group compared to the delayed group. AUTHORS' CONCLUSIONS: For many clinical outcomes, there were no differences between prescribing strategies. Symptoms for acute otitis media and sore throat were modestly improved by immediate antibiotics compared with delayed antibiotics. There were no differences in complication rates. Delaying prescribing did not result in significantly different levels of patient satisfaction compared with immediate provision of antibiotics (86% versus 91%; moderate-certainty evidence). However, delay was favoured over no antibiotics (87% versus 82%). Delayed antibiotics achieved lower rates of antibiotic use compared to immediate antibiotics (30% versus 93%). The strategy of no antibiotics further reduced antibiotic use compared to delaying prescription for antibiotics (13% versus 27%). Delayed antibiotics for people with acute respiratory infection reduced antibiotic use compared to immediate antibiotics, but was not shown to be different to no antibiotics in terms of symptom control and disease complications. Where clinicians feel it is safe not to prescribe antibiotics immediately for people with RTIs, no antibiotics with advice to return if symptoms do not resolve is likely to result in the least antibiotic use while maintaining similar patient satisfaction and clinical outcomes to delayed antibiotics. Where clinicians are not confident in not prescribing antibiotics, delayed antibiotics may be an acceptable compromise in place of immediate prescribing to significantly reduce unnecessary antibiotic use for RTIs, while maintaining patient safety and satisfaction levels. Further research into antibiotic prescribing strategies for RTIs may best be focused on identifying patient groups at high risk of disease complications, enhancing doctors' communication with patients to maintain satisfaction, ways of increasing doctors' confidence to not prescribe antibiotics for RTIs, and policy measures to reduce unnecessary antibiotic prescribing for RTIs.

Occupation and occurrence of respiratory infections among adults with newly diagnosed asthma.

BACKGROUND: Work environments are potential areas for spreading respiratory infections. We hypothesized that certain occupations increase susceptibility to respiratory infections among adults with asthma. Our objective was to compare the occurrence of respiratory infections among different occupations in adults with newly diagnosed asthma. METHODS: We analysed a study population of 492 working-age adults with newly diagnosed asthma who were living in the geographically defined Pirkanmaa Area in Southern Finland during a population-based Finnish Environment and Asthma Study (FEAS). The determinant of interest was occupation at the time of diagnosis of asthma. We assessed potential relations between occupation and occurrence of both upper and lower respiratory tract infections during the past 12 months. The measures of effect were incidence rate ratio (IRR) and risk ratio (RR) adjusted for age, gender, and smoking habits. Professionals, clerks, and administrative personnel formed the reference group. RESULTS: The mean number of common colds in the study population was 1.85 (95% CI 1.70, 2.00) infections in the last 12 months. The following occupational groups showed increased risk of common colds: forestry and related workers (aIRR 2.20, 95% CI 1.15-4.23) and construction and mining (aIRR 1.67, 95% CI 1.14-2.44). The risk of lower respiratory tract infections was increased in the following groups: glass, ceramic, and mineral workers (aRR 3.82, 95% CI 2.54-5.74), fur and leather workers (aRR 2.06, 95% CI 1.01-4.20) and metal workers (aRR 1.80, 95% CI 1.04-3.10). CONCLUSIONS: We provide evidence that the occurrence of respiratory infections is related to certain occupations.

The conceptualization of acute bronchitis in general practice - a fuzzy problem with consequences? A qualitative study in primary care.

BACKGROUND: Acute bronchitis is one of the most frequent diagnoses in primary care. Scientifically, it is conceptualized as a viral infection. Still, general practitioners (GPs) often prescribe antibiotics for acute bronchitis. The explanation for this discrepancy may lie in a different conceptualization of acute bronchitis. Therefore, we wanted to know, how GPs conceptualize acute bronchitis, and how they differentiate it from common cold and pneumonia. Furthermore, we tried to find out the GPs' reasons for prescribing antibiotics in those cases. METHODS: To answer our study questions, we conducted a qualitative study with GPs in Bavaria, Germany, by using semi-structured guided interviews. The analysis of the data was conducted using the documentary method according to Ralf Bohnsack. The transcripts were subdivided into categories. Analyzing each part by reflective interpretation, first manually, secondly with the help of RQDA, we extracted the most representative citations and main messages from the interviews. RESULTS: The term acute bronchitis seems to be applied when there is neither certainty of the diagnosis common cold, nor of pneumonia. It seems it bridges the gap of uncertainty between supposedly harmless clinical pictures (common cold/viral), to the more serious ones (pneumonia/bacterial). The conceptual transitions between common cold and acute bronchitis on the one side, and acute bronchitis and pneumonia on the other are fluid. The diagnosis acute bronchitis cannot solve the problem of uncertainty but seems to be a label to overcome it by offering a way to include different factors such as severity of symptoms, presumed signs of bacterial secondary infection, comorbidities, and presumed expectations of patients. It seems to solve the pathophysiologic riddle of bacterial or viral and of decision making in prescribing antibiotics. CONCLUSION: Acute bronchitis as an "intermediate category" proved difficult to define for the GPs. Applying this diagnosis leaves GPs in abeyance of prescribing an antibiotic or not. As a consequence of this uncertainty in pathophysiologic reasoning (viral or bacterial) other clinical and social factors tip the balance towards antibiotic prescribing. Teaching physicians to better think in probabilities of outcomes instead of pathophysiologic reasoning and to deal with uncertainty might help reducing antibiotic overprescribing.

Adherence to CPAP in summer to autumn predicts self-reported common cold symptoms in patients with obstructive sleep apnea in winter: A prospective observational study.

OBJECTIVE: We conducted a prospective observational study to determine the relationship between adherence to continuous positive airway pressure (CPAP) and susceptibility to the common cold in moderate-to-severe obstructive sleep apnea (OSA) patients. METHODS: We prospectively investigated the number of days with common cold symptoms from November 2019 to February 2020. The rate of CPAP use for 4 h/night in the preceding four months (July to October 2019) was used as a measure of CPAP adherence. Multiple generalized linear models were used to evaluate the association to days of common cold symptoms after controlling for demographic variables, habitual short sleep duration, and insomnia severity. RESULTS: We included 123 outpatients (median age 63 years) with moderate-to-severe OSA treated with CPAP. In the multivariate generalized linear model, better CPAP adherence was independently significantly associated with days with fewer common cold symptoms (ß = -0.248, P = 0.031); meanwhile, the severity of insomnia and habitual short sleep duration was not significantly associated with it. Subgroup analyses revealed that the association between CPAP adherence and days with common cold symptoms was also significant in young to middle-aged (<65 years) participants (ß = -0.407, P = 0.005). In contrast, the association was negligible in older (≥65 years) participants. CONCLUSIONS: CPAP adherence may be protective against viral infections in patients with moderate-to-severe OSA. This effect appears to be more pronounced in young to middle-aged patients with OSA.

Early intervention with ColdZyme mouth spray after self-diagnosis of common cold: A randomized, double-blind, placebo-controlled study.

BACKGROUND: Previous clinical and in vitro investigations have supported the efficacy of a glycerol throat spray containing cold-adapted cod trypsin (ColdZyme) against respiratory viruses causing the common cold bycreating a protective mucosal barrier shown to deactivate common cold virus in vitro and decrease pharyngeal rhinovirus load. METHODS AND FINDINGS: This was a double-blind, randomized, parallel-group, placebo-controlled study conducted at 10 German sites to evaluate the efficacy of the medical device ColdZyme, a glycerol mouth spray containing cold-adapted cod trypsin for a naturally occurring common cold versus placebo spray. Adults experiencing a minimum of three common colds during the previous year, but otherwise healthy, were enrolled to begin treatment with the mouth spray or placebo six times daily at first sign of a common cold. Jackson's symptom scale and the 9-item Wisconsin Upper Respiratory Symptom Survey-21 (WURSS-21) quality of life (QoL) domain and a sore throat scale were recorded daily by subjects, as well as any use of allowed rescue treatment. Between January and April 2019, 701 subjects were enrolled and randomly assigned to the ColdZyme group (n = 351) or the placebo group (n = 350). Of the 701 subjects, 438 (62.5%) subjects developed symptoms typical of common cold, and all 438 started study treatment (n = 220 in the ColdZyme group and n = 218 in the placebo group). The demographic profile of the treatment groups were comparable with 68.1% female and almost all subjects being Caucasian (98.4%). The age ranged between 18 and 70 years with a mean age of 41.3 (±14.4) years. There were no differences between the groups in primary and major secondary endpoints, however, the assessment using the WURSS-21 QoL domain and Jackson score suggests a slightly faster recovery with ColdZyme as symptoms and complaints affecting the quality of life were shortened by about 1 day. The beneficial effect of ColdZyme was particularly noticeable on the fifth day of the common cold. A positive difference between treatment groups was also seen for the subjects' assessments of global efficacy of the investigational product A robust safety profile for ColdZyme was demonstrated throughout the study. CONCLUSION: The safety and tolerability of ColdZyme have been confirmed in a large study population and further establishes evidence of a faster recovery from common cold symptoms. Early self-diagnosis and early use of ColdZyme mouth spray is a safe alternative for treatment of naturally occurring colds.

Maternal Common Cold or Fever During Pregnancy and the Risk of Orofacial Clefts in the Offspring: A Systematic Review and Meta-analysis.

The common cold and/or an associated fever during pregnancy have/has been suspected to harm the developing fetus. We sought possible correlations between a maternal common cold or fever during pregnancy and the risk of orofacial clefts in the offspring.We systematically searched PubMed and Embase using appropriate keywords, and we checked the reference lists of retrieved articles. We used random-effects models to estimate overall relative risks.Incidence of orofacial clefts.We included 13 case-control studies. Modest but statistically significant associations were found between a maternal common cold and cleft lip with or without a cleft palate (CL/CP) (odds ratio [OR] 2.17; 95% confidence interval [CI] 1.66-2.83) and a cleft palate only (CPO) (OR 3.08; 95% CI 1.5-6.34). Furthermore, maternal fever was also associated with an increased risk of CL/CP (OR 1.91, 95% CI 1.3-2.8) and CPO (OR 1.48, 95% CI 0.83-2.63) in the offspring. Further analyses of maternal influenza (alone) yielded similar results.Although evidence of heterogeneity should be carefully evaluated, our findings suggest that maternal common cold or fever during pregnancy may be associated with a greater risk of CL/CP or CPO in the offspring. Future cohort studies using valid assessments of maternal common cold exposure during pregnancy that consider the severity of fever are needed to clarify the contribution of maternal common cold or fever status to the risk of orofacial clefts in children.

Incidence rate, risk factors, and management of Bell's palsy in the Qurayyat region of Saudi Arabia.

Background: Bell's palsy is an idiopathic facial nerve dysfunction causing temporary paralysis of muscles of facial expression. This study aimed to determine the incidence rate, common risk factors, and preferred treatment by the Saudi patients with Bell's palsy. Method: This cross-sectional study was carried out in the Qurayyat region of Saudi Arabia. The retrospective medical records were searched from 2015-2020 of patients diagnosed with Bell's palsy at Qurayyat General Hospital and King Fahad hospital. A 28-item questionnaire was developed by a team of experts and pre-tested among patients with Bell's palsy before being sent to the eligible participants. The data were analyzed using summary statistics, Chi-square test, Fisher exact test and Likelihood ratio test. Results: We identified 279 cases of Bell's palsy from the medical records of the hospitals from the years 2015 to 2020, accounting for 46.5 cases per year and an incidence rate of 25.7 per 100,000 per year. Out of 279 patients with Bell's palsy, only 171 returned the questionnaire accounting for a response rate of 61.2%. Out of 171 patients with Bell's palsy, females (n = 147, 86.0%) accounted for the majority of cases. The most affected age group among participants with Bell's palsy was 21-30 years (n = 76, 44.4%). There were 153 (89.5%) cases who reported Bell's palsy for the first time. The majority of the participants experienced right-sided facial paralysis (n = 96, 56.1%). Likelihood ratio test revealed significant relationship between exposure to cold air and common cold with age groups (χ 2(6, N = 171) = 14.92, p = 0.021), χ 2(6, N = 171) = 16.35, pp = 0.012 respectively. The post hoc analyses revealed that participants in the age group of 20-31-years were mostly affected due to exposure to cold air and common cold than the other age groups. The main therapeutic approach preferred was physiotherapy (n = 149, 87.1%), followed by corticosteroids and antivirals medications (n = 61, 35.7%), acupressure (n = 35, 20.5%), traditional Saudi herb medicine (n = 32, 18.7%), cauterization by hot iron rod (n = 23, 13.5%), supplementary therapy (n = 2, 1.2%), facial cosmetic surgery (n = 1, 0.6%) and no treatment (n = 1, 0.6%). The most preferred combined therapy was physiotherapy (87.6%) with corticosteroid and antiviral drugs (35.9%), and acupressure (17.6%). Conclusion: The rate of Bell's palsy was approximately 25.7 per 100,000 per year in the Qurayyat region of Saudi Arabia. Exposure to cold air and common cold were the significant risk factors associated with Bell's palsy. Females were predominantly affected by Bell's palsy in the Qurayyat region of Saudi Arabia. Bell's palsy most commonly occurred in the age group 21-30 years. The most favored treatment was physiotherapy following Bell's palsy.

[A CASE OF STEVENS-JOHNSON SYNDROME SUSPECTED BY A COMMON COLD MEDICATION AS CAUSE].

We describe here the case of a 7-year-old male patient with Stevens-Johnson syndrome (SJS), which was suspected to be caused by treatment with tipepidine hibenzate (Asverin®). The day after taking tipepidine hibenzate and L-carbocysteine (Carbocysteine® DS) for relief of a cold, he began presenting with the following symptoms: fever above 38°C, wheezing, and decreased oxygen saturation. Two days later, mucous membrane rashes, such as erosions on the lips, eye mucosa, vulva, and blisters on the trunk appeared, and SJS was thus diagnosed. Because pseudomembrane formation and corneal epithelial defect in the eyes were also observed, steroid pulse therapy was administered early in the course of the disease, and the patient recovered without sequelae.A drug-induced lymphocyte stimulation test performed to determine the cause of the disease was positive for fixed-dose combination therapy with tipepidine hibenzate plus L-carbocysteine and for tipepidine hibenzate alone. It has now been three years since the onset of the disease, and no sequelae have been observed. Although tipepidine hibenzate is a drug frequently used for pediatric patients, it should be administered with caution because of its potential to cause SJS.

A severe case of human coronavirus 229E pneumonia in an elderly man with diabetes mellitus: a case report.

BACKGROUND: With pandemic of coronavirus disease 2019 (COVID-19), human coronaviruses (HCoVs) have recently attached worldwide attention as essential pathogens in respiratory infection. HCoV-229E has been described as a rare cause of lower respiratory infection in immunocompetent adults. CASE PRESENTATION: We reported a 72-year-old man infected by HCoV-229E with rapid progression to acute respiratory distress syndrome, in conjunction with new onset atrial fibrillation, intensive care unit acquired weakness, and recurrent hospital acquired pneumonia. Clinical and radiological data were continuously collected. The absolute number of peripheral T cells and the level of complement components diminished initially and recovered after 2 months. The patient was successfully treated under intensive support care and discharged from the hospital after 3 months and followed. CONCLUSION: HCoV-229E might an essential causative agent of pulmonary inflammation and extensive lung damage. Supportive treatment was essential to HCoVs infection on account of a long duration of immunological recovery in critical HCoV-229E infection.

Ivacaftor or lumacaftor/ivacaftor treatment does not alter the core CF airway epithelial gene response to rhinovirus.

BACKGROUND: Aberrant responses by the cystic fibrosis airway epithelium during viral infection may underly the clinical observations. Whether CFTR modulators affect antiviral responses by CF epithelia is presently unknown. We tested the hypothesis that treatment of CF epithelial cells with ivacaftor (Iva) or ivacaftor/lumacaftor (Iva/Lum) would improve control of rhinovirus infection. METHODS: Nineteen CF epithelial cultures (10 homozygous for p.Phe508del as CFTR Class 2, 9 p.Phe508del/p.Gly551Asp as Class 3) were infected with rhinovirus 1B at multiplicity of infection 12 for 24 h. Culture RNA and supernatants were harvested to assess gene and protein expression respectively. RESULTS: RNA-seq analysis comparing rhinovirus infected cultures to control identified 796 and 629 differentially expressed genes for Class 2 and Class 3, respectively. This gene response was highly conserved when cells were treated with CFTR modulators and were predicted to be driven by the same interferon-pathway transcriptional regulators (IFNA, IFNL1, IFNG, IRF7, STAT1). Direct comparisons between treated and untreated infected cultures did not yield any differentially expressed genes for Class 3 and only 68 genes for Class 2. Changes were predominantly related to regulators of lipid metabolism and inflammation, aspects of epithelial biology known to be dysregulated in CF. In addition, CFTR modulators did not affect viral copy number, or levels of pro-inflammatory cytokines produced post-infection. CONCLUSIONS: Though long-term clinical data is not yet available, results presented here suggest that first generation CFTR modulators do not interfere with core airway epithelial responses to rhinovirus infection. Future work should investigate the latest triple modulation therapies.

Rhinovirus and asthma: Challenges and opportunities.

Human rhinoviruses (RVs) are the primary aetiological agent of the common cold. Generally, the associated infection is mild and self-limiting, but may also be associated with bronchiolitis in infants, pneumonia in the immunocompromised and exacerbation in patients with pulmonary conditions such as asthma or chronic obstructive pulmonary disease. Viral infection accounts for as many as two thirds of asthma exacerbations in children and more than half in adults. Allergy and asthma are major risk factors for more frequent and severe RV-related illnesses. The prevalence of RV-induced wheezing will likely continue to increase given that asthma affects a significant proportion of the population, with allergic asthma accounting for the majority. Several new respiratory viruses and their subgroups have been discovered, with various degrees of relevance. This review will focus on RV infection in the context of the epidemiologic evidence, genetic variability, pathobiology, clinical studies in the context of asthma, differences with other viruses including COVID-19 and current treatment interventions.

Integrated-omics endotyping of infants with rhinovirus bronchiolitis and risk of childhood asthma.

BACKGROUND: Young children with rhinovirus (RV) infection-particularly bronchiolitis-are at high risk for developing childhood asthma. Emerging evidence suggests clinical heterogeneity within RV bronchiolitis. However, little is known about these biologically distinct subgroups (endotypes) and their relations with asthma risk. OBJECTIVE: We aimed to identify RV bronchiolitis endotypes and examine their longitudinal relations with asthma risk. METHODS: As part of a multicenter prospective cohort study of infants (age <12 months) hospitalized for bronchiolitis, we integrated clinical, RV species (RV-A, RV-B, and RV-C), nasopharyngeal microbiome (16S rRNA gene sequencing), cytokine, and metabolome (liquid chromatography tandem mass spectrometry) data collected at hospitalization. We then applied network and clustering approaches to identify bronchiolitis endotypes. We also examined their longitudinal association with risks of developing recurrent wheeze by age 3 years and asthma by age 5 years. RESULTS: Of 122 infants hospitalized for RV bronchiolitis (median age, 4 months), we identified 4 distinct endotypes-mainly characterized by RV species, microbiome, and type 2 cytokine (T2) response: endotype A, virusRV-CmicrobiomemixedT2low; endotype B, virusRV-AmicrobiomeHaemophilusT2low; endotype C, virusRSV/RVmicrobiomeStreptococcusT2low; and endotype D, virusRV-CmicrobiomeMoraxellaT2high. Compared with endotype A infants, endotype D infants had a significantly higher rate of recurrent wheeze (33% vs 64%; hazard ratio, 2.23; 95% CI, 1.00-4.96; P = .049) and a higher risk for developing asthma (28% vs 59%; odds ratio, 3.74: 95% CI, 1.21-12.6; P = .03). CONCLUSIONS: Integrated-omics analysis identified biologically meaningful RV bronchiolitis endotypes in infants, such as one characterized by RV-C infection, Moraxella-dominant microbiota, and high T2 cytokine response, at higher risk for developing recurrent wheeze and asthma. This study should facilitate further research toward validating our inferences.

Comparison of COVID-19 and common cold chemosensory dysfunction.

Anosmia constitutes a prominent symptom of COVID-19. However, anosmia is also a common symptom of acute colds of various origins. In contrast to an acute cold, it appears from several questionnaire-based studies that in the context of COVID-19 infection, anosmia is the main rhinological symptom and is usually not associated with other rhinological symptoms such as rhinorrhoea or nasal obstruction. Until now, no study has directly compared smell and taste function between COVID-19 patients and patients with other causes of upper respiratory tract infection (URTI) using valid and reliable psychophysical tests. In this study, we aimed to objectively assess and compare olfactory and gustatory functions in 10 COVID-19 patients (PCR diagnosed, assessed on average 2 weeks after infection), 10 acute cold (AC) patients (assessed before the COVID-19 outbreak) and 10 healthy controls, matched for age and sex. Smell performance was assessed using the extended "Sniffin' Sticks" test battery (4), while taste function was assessed using "taste strips" (5). Receiver Operating Characteristic (ROC) curves were built to probe olfactory and gustatory scores in terms of their discrimination between COVID-19 and AC patients. Our results suggest that mechanisms of COVID-19 related olfactory dysfunction are different from those seen in an AC and may reflect, at least to some extent, a specific involvement at the level of central nervous system in some COVID-19 patients. In the future, studies to assess the prevalence of persistent anosmia and neuroanatomical changes on MRI correlated to chemosensory function, will be useful to understand these mechanisms.

The efficacy of a compounded micronutrient supplement on the incidence, duration, and severity of the common cold: A pilot randomized, double-blinded, placebo-controlled trial.

PURPOSE: Viral upper respiratory infections are associated with significant health and economic impact. This study sought to determine the efficacy of routine immune system micronutrient supplementation on the incidence, duration and severity of common cold symptoms. METHODS: This pilot study was a randomized, double-blinded, placebo-controlled trial of N = 259 with asymptomatic participants aged 18 to 65 in two cold seasons of 2016 and 2017. The treatment group received an immune system targeted micronutrient caplet, while the placebo group received a micronized cellulose caplet externally identical to the treatment caplet. Weekly surveys were sent electronically to participants to document common cold incidence, duration and severity. Primary statistical results were obtained using mixed-effects logistic regressions to account for longitudinal measurements for participants. RESULTS: The odds of acquiring an upper respiratory infection, adjusted for potential confounders, was estimated to be 0.74 times lower in the treatment group (p = 0.14). The odds of reporting specific symptoms were statistically lower in the treatment arm compared to the placebo arm for runny nose (OR = 0.53, p = 0.01) and cough (OR = 0.51, p = 0.04). Shorter durations of runny nose and cough were also observed in the treatment arm compared to placebo (both p < 0.05). There was no significant difference in severity of symptoms in either group. The observed proportion of reported cold symptoms in the treatment group was lower compared to the placebo group between late January and February in two consecutive cold seasons. Given the physical, workplace and economic impact of upper respiratory infections, this low cost and low risk intervention should be further studied with more robust investigation and meticulous experimental design.

Rhinovirus Infection Is Associated With Airway Epithelial Cell Necrosis and Inflammation via Interleukin-1 in Young Children With Cystic Fibrosis.

Introduction: The responses of cystic fibrosis (CF) airway epithelial cells (AEC) to rhinovirus (RV) infection are likely to contribute to early pathobiology of lung disease with increased neutrophilic inflammation and lower apoptosis reported. Necrosis of AEC resulting in airway inflammation driven by IL-1 signaling is a characteristic finding in CF detectable in airways of young children. Being the most common early-life infection, RV-induced epithelial necrosis may contribute to early neutrophilic inflammation in CF via IL-1 signaling. As little is known about IL-1 and biology of CF lung disease, this study assessed cellular and pro-inflammatory responses of CF and non-CF AEC following RV infection, with the hypothesis that RV infection drives epithelial necrosis and IL-1 driven inflammation. Methods:Primary AEC obtained from children with (n = 6) and without CF (n = 6) were infected with RV (MOI 3) for 24 h and viable, necrotic and apoptotic events quantified via flow cytometry using a seven-step gating strategy (% total events). IL-1α, IL-1ß, IL-1Ra, IL-8, CXCL10, CCL5, IFN-ß, IL-28A, IL-28B, and IL-29 were also measured in cell culture supernatants (pg/mL). Results:RV infection reduced viable events in non-CF AEC (p < 0.05), increased necrotic events in non-CF and CF AEC (p < 0.05) and increased apoptotic events in non-CF AEC (p < 0.05). Infection induced IL-1α and IL-1ß production in both phenotypes (p < 0.05) but only correlated with necrosis (IL-1α: r = 0.80; IL-1ß: r = 0.77; p < 0.0001) in CF AEC. RV infection also increased IL-1Ra in non-CF and CF AEC (p < 0.05), although significantly more in non-CF AEC (p < 0.05). Finally, infection stimulated IL-8 production in non-CF and CF AEC (p < 0.05) and correlated with IL-1α (r = 0.63 & r = 0.74 respectively; p < 0.0001). Conclusions:This study found RV infection drives necrotic cell death in CF AEC. Furthermore, RV induced IL-1 strongly correlated with necrotic cell death in these cells. As IL-1R signaling drives airway neutrophilia and mucin production, these observations suggest RV infection early in life may exacerbate inflammation and mucin accumulation driving early CF lung disease. Since IL-1R can be targeted therapeutically with IL-1Ra, these data suggest a new anti-inflammatory therapeutic approach targeting downstream effects of IL-1R signaling to mitigate viral-induced, muco-inflammatory triggers of early lung disease.