Common cold.

The common cold is a unique human disease, as it is arguably the most common disease and because of the large number of respiratory viruses causing colds it is one of the most complex of human diseases. This review discusses the respiratory viruses and notes that all these viruses may cause the illness complex recognised as the common cold. The common cold is discussed as part of the "iceberg concept" of disease which ranges from asymptomatic infection to severe illness and death. The factors influencing the incidence of colds are discussed: crowding and sociability, stress, smoking and alcohol, immune status, sex, age, sleep, season, chilling, nutrition and exercise. The mechanism of symptoms related to the innate immune response is explained and symptomatic treatments are tabulated. Morbidity associated with common cold is discussed and possible vaccines.

Treatment of COVID-19 symptoms with over the counter (OTC) medicines used for treatment of common cold and flu.

Persons suffering from acute upper respiratory tract viral infections (URTI) commonly use over the counter (OTC) medicines to relieve symptoms such as fever, muscle aches, cough, runny nose, sore throat and nasal congestion. At present OTC medicines are only licensed for treatment of common cold and flu symptoms and not for treatment of the same symptoms associated with COVID-19. The innate immune response responsible for the mechanisms of the symptoms of URTI is the same for all respiratory viruses including SARS-CoV-2 and these symptoms can be relieved by treatment with the same OTC medicines as available for treatment of colds and flu. This review provides scientific information that OTC treatments for common cold and flu-like illness caused by respiratory viruses are safe and effective treatments for the same symptoms associated with COVID-19.

Management of acute upper respiratory tract infection: the role of early intervention.

INTRODUCTION: Upper respiratory tract infection (URTI) is an illness caused by an acute infection by viruses or bacteria of the nose, sinuses, pharynx, and larynx. Most URTIs are short, mild, and self-limiting, but some can lead to serious complications, resulting in heavy social and economic burden on individuals and society. AREAS COVERED: This article presents the management guidelines and consensus established through the Delphi method during an expert roundtable conducted in November 2020 and results of a targeted literature review. EXPERT OPINION: The current acute URTI management strategies aim toward symptom alleviation and prevention of URTI virus transmission. The effectiveness of these strategies is highly increased with early intervention, administered prior to the peaking of viral shedding. This reduces the chances of developing a full-blown acute URTI, decreases symptom severity, and reduces viral transmission. Mucoadhesive gel nasal sprays have shown promising results for early intervention of acute URTI. They act by creating a barrier that can trap virus particles, thereby preventing invasion of the mucosa by the virus. Additionally, they deliver broad spectrum activity that is effective against a wide variety of pathogens that cause acute URTI. Acute URTI warrants greater attention and proactive management in reducing its burden.

Placebo and Side Effects Confound Clinical Trials on New Antitussives.

This review discusses how the placebo effect related to treatment side effects may confound clinical trials on antitussives and specifically looks at the implications for trials on ATP antagonists. These new antitussives have distinctive side effects on the sensation of taste, and investigators have expressed concerns that this may unblind the clinical trials. Blinding is an essential component of trial design, but the degree of blinding in trials is rarely assessed. The assumptions of additivity and balance in clinical trials are discussed as important factors that allow assessment of the pharmacological activity of an antitussive. How side effects unbalance a clinical trial by amplifying the placebo effect of active treatments is discussed. The point is made that unblinding of trials invalidates any assessment of efficacy but that there is little interest or discussion about this fundamental aspect of trials. Proposals are discussed which may improve the blinding of trials and control placebo effects by changes to participant information, trial design, patient selection and use of active placebos. The issue of unblinding of clinical trials is not a new issue, but if real progress is to be made in developing new antitussives, then it is an issue that needs to be urgently addressed.

Why is temperature sensitivity important for the success of common respiratory viruses?

This review explores the idea that temperature sensitivity is an important factor in determining the success of respiratory viruses as human parasites. The review discusses several questions. What is viral temperature sensitivity? At what range of temperatures are common respiratory viruses sensitive? What is the mechanism for their temperature sensitivity? What is the range of temperature along the human airway? What is it that makes respiratory viruses such successful parasites of the human airway? What is the role of temperature sensitivity in respiratory zoonoses? A definition of temperature sensitivity is proposed, as "the property of a virus to replicate poorly or not at all, at the normal body temperature of the host (restrictive temperature), but to replicate well at the lower temperatures found in the upper airway of the host (permissive temperature)." Temperature sensitivity may influence the success of a respiratory virus in several ways. Firstly; by restricting the infection to the upper airways and reducing the chance of systemic infection that may reduce host mobility and increase mortality, and thus limit the spread of the virus. Secondly; by causing a mild upper airway illness with a limited immune response compared to systemic infection, which means that persistent herd immunity does not develop to the same extent as with systemic infections, and re-infection may occur later. Thirdly; infection of the upper airway triggers local reflex rhinorrhea, coughing and sneezing which aid the exit of the virus from the host and the spread of infection in the community.

The role of nasal congestion as a defence against respiratory viruses.

INTRODUCTION: This review discusses how nasal congestion may have benefits as a mechanism of defence against respiratory viruses. METHODS: A literature research was conducted on respiratory viruses and nasal congestion, following a recently published review on how temperature sensitivity is important for the success of common respiratory viruses. RESULTS: The literature reported that common respiratory viruses are temperature sensitive and replicate well at the cooler temperatures of the upper airways (32°C), but replication is restricted at body temperature (37°C). The amplitude of the phases of congestion and decongestion associated with the nasal cycle was increased on infection with respiratory viruses and this caused unilateral nasal congestion and obstruction. Nasal congestion and obstruction increase nasal mucosal temperature towards 37°C and therefore restricted the replication of respiratory viruses. CONCLUSION: Nasal congestion associated with the nasal cycle may act as a mechanism of respiratory defence against infection with respiratory viruses.

What is the Role of Over 100 Excipients in Over the Counter (OTC) Cough Medicines?

Most medicines are white bitter powders that are formulated as tablets and capsules but cough medicines are an exception where the taste and appearance of the medicine are more important to the patient than the pharmacology of the active ingredient. Excipients are generally defined as any ingredient in a medicine other than the active ingredient. In most medicines excipients play a supportive role in delivering the medicine, but in the case of cough medicines, excipients have more important and complex roles and they can also be the main active ingredient of the cough medicine as menthol, glycerol, and sugars, which are declared as active ingredients. This review searched the United Kingdom electronic medicines compendium (emc) and found over 100 excipients in 60 different liquid formulations of over the counter cough medicines. The excipients were divided into functional groups: sweeteners, thickeners, flavors, colors, antimicrobials, and buffers, and the incidence and function of the different excipients is discussed. When considering the efficacy of a cough medicine, clinicians and pharmacists tend to think of the pharmacology of antitussives such as dextromethorphan or expectorants such as guaifenesin, and they rarely consider the role of excipients in the efficacy of the medicine. This review discusses the functions and importance of excipients in cough medicines and provides some new information for clinicians, pharmacists, and all interested in the treatment of cough when considering the composition and efficacy of a cough medicine.

Observational study of the effects of upper respiratory tract infection on hydration status.

BACKGROUND: A frequent treatment recommendation during acute respiratory infection is to increase fluid intake. This is the first study to investigate whether upper respiratory tract infections (URTIs) such as common cold can lead to dehydration, as commonly believed by the public. METHODS: This was an exploratory, noninterventional, observational, single-center study. Subjects made 2 visits to a UK study center for assessments of dehydration, once during URTI and then 2-3 weeks later when fully recovered. The primary endpoint was a comparison of serum osmolality during vs after URTI. Complete blood count, serum urea, serum electrolytes, urine parameters (eg, osmolality, specific gravity, color), body weight/BMI, subjective assessment of thirst, and physician assessment of dehydration were additional outcomes. Only descriptive statistics and shift tables were used. RESULTS: Fifty-five otherwise healthy adults with moderate to severe URTI of < 120 h in duration were enrolled (63.6% female, 94.5% white, mean [SD] age 21.0 [6.8] years). There was no evidence of dehydration based on serum osmolality (mean [SD] 287.63 [4.83] mosm/kg during URTI; 288.60 [5.99] mosm/kg after recovery). With only a few exceptions, complete blood count, serum urea, serum electrolytes, urine specific gravity, urine color, and physician ratings of hydration remained stable. Body weight decreased > 1% in 34.0% of subjects and increased > 1% in 17.0% between visits, with similar changes in BMI. Urine osmolality varied: 14 subjects showed a decrease and 5 showed an increase, resulting in a higher mean [SD] urine osmolality during URTI (700.50 [231.59] vs 618.47 [320.29] mosm/kg). Subjects perceived greater thirst during URTI. CONCLUSIONS: In this pilot observational study, we found no evidence that URTIs such as common cold are associated with dehydration, contrary to popular belief.

Soothing Properties of Glycerol in Cough Syrups for Acute Cough Due to Common Cold.

The treatment and management of acute cough due to common cold costs billions of dollars of healthcare expenditure and there is a growing opinion that a simple linctus containing glycerol with flavourings such as honey and lemon is a safe and effective treatment for acute cough in children and adults. Glycerol is a component of most cough syrups, and although it is often thought of only as a solvent or thickening agent in cough syrups, it may be a major component for the efficacy of cough syrups due to its special properties of lubrication, demulcency, sweetness, and acting as a humectant. The major benefit of cough syrups in soothing cough is likely due to the properties of the syrup rather than the active ingredients and this review discusses the special properties of glycerol in relation to the treatment of acute cough.

Treatment of Acute Cough Due to the Common Cold: Multi-component, Multi-symptom Therapy is Preferable to Single-Component, Single-Symptom Therapy--A Pro/Con Debate.

Acute viral upper respiratory tract infection, or, the common cold, affects essentially every human being, and cough is reported as its most frequent associated symptom. Billions of dollars are spent worldwide annually by individuals seeking relief from this multi-symptom syndrome. Thousands of non-prescription, over-the-counter products are available worldwide, aimed at relieving the various bothersome symptoms induced by the common cold. Differences of opinion exist as to whether optimal therapy for cough associated with the common cold consists of multi-component, multi-symptom cough/cold preparations, or, whether single-component medications, aimed at relief of specific symptoms, represent the optimal therapeutic approach. The 5th American Cough Conference, held in Washington, D.C. in June, 2015, provided an ideal forum for discussion and debate of this issue between two internationally recognized experts in the field of the common cold and its treatment.

The nasal cycle and age.

CONCLUSION: The reciprocal nature of the nasal cycle declined with age in keeping with other published data, suggesting that studies of the nasal cycle may be a useful measure of central nervous system (CNS) disease and aging. OBJECTIVES: The aim of this study was to investigate changes in the nasal cycle with age. METHODS: In one male subject changes in nasal airflow were measured by anterior rhinomanometry to determine the reciprocal nature of the 'nasal cycle' at age 28 and again at age 66 years. RESULTS: Significant reciprocity was demonstrated in the historical study (age 28 years) with correlation coefficients for the 3 study days of -0.81, -0.83 and -0.79. compared with the current study (age 66 years) where non-significant correlation coefficients of 0.02 and -0.43 were obtained.

Analgesic and Decongestant Efficacy of the Combination of Aspirin with Pseudoephedrine in Patients With Symptoms of Upper Respiratory Tract Infection.

The study investigated the efficacy and safety of a combination therapy of 1,000 mg aspirin (ASA) and 60 mg pseudoephedrine (PSE) on the symptoms of pain (combined score for headache and sore throat) and nasal congestion in 833 patients with acute upper respiratory tract viral infection (URTI), over 4 hours after a single dose in the clinic and over 3 days with multiple doses at home. The study demonstrated that over 4 hours in the clinic the combination ASA plus PSE was superior to PSE or placebo for relief of pain symptoms measured subjectively with pain scores, and was superior to ASA or placebo for relief of nasal congestion as measured objectively with rhinomanometry and subjectively with congestion scores. After 3 days of treatment, ASA plus PSE was superior to PSE but not to placebo or ASA for global pain assessments, and ASA plus PSE was superior to ASA and placebo but not to PSE for congestion assessments. No unexpected adverse events occurred and no serious adverse events were attributed to study medicines. This study demonstrates that a combination therapy of ASA plus PSE provides safe and effective relief of both common cold pain related symptoms and nasal congestion.

Perfil de eficacia y seguridad de Echinacea purpurea en la prevención de episodios de resfriado común: estudio clínico aleatorizado, doble ciego y controlado con placebo / Safety and efficacy profile of Echinacea purpurea to prevent common cold episodes: a randomized, double-blind, placebo-controlled trial

Objetivo: Investigar la seguridad y la eficacia de un extracto de Echinacea purpurea en la prevención del resfriado común en una amplia población durante un período de 4 meses. Método: 755 sujetos sanos recibieron un extracto etanólico de E. purpurea(95% parte aérea florida y 5% de raíz) fresca o placebo. A los participantes se les solicitó registrar en un diario los acontecimientos adversos y evaluar los síntomas relacionados con el resfriado, durante todo el período del estudio. Se tomaron muestras de las secreciones nasales de los participantes que padecieron resfriados agudos y fueron examinadas en busca de virus. Resultados: Ocurrieron un total de 293 acontecimientos adversos en el grupo al que se le asignó la equinácea y 306 en el grupo placebo. El 9% de los participantes experimentó acontecimientos adversos, que se consideraron al menos posiblemente, relacionados con el extracto (reacciones adversas), frente al 10% en el grupo placebo. Por lo tanto, la seguridad de la equinácea no fue inferior a la del placebo. La equinácea redujo el número total de episodios de resfriados, los días acumulados de resfriado y los episodios comedicados con analgésicos y antiinflamatorios. Asimismo inhibió los resfriados virales confirmados por deteccion del virus y previno especialmente las infecciones de los virus con membrana (p<0,05) La equinácea demostró mayor eficacia en las infecciones recurrentes y los efectos preventivos aumentaron cuando se cumplió estrictamente con el tratamiento y con el protocolo. Conclusión: La toma profiláctica de E. purpurea durante un período de 4 meses proporcionó una relación beneficio/riesgo positiva (AU)

Objective: To investigate the safety (risk) and efficacy (benefit) of Echinacea purpurea extract in the prevention of common cold episodes in a large population over a 4-month period. Methods: 755 healthy subjects were allocated to receive either an alcohol extract from freshly harvested E. purpurea (95% herba and 5% root) or placebo. Participants were required to record adverse events and to rate cold-related issues in a diary throughout the investigation period. Nasal secretions were sampled at acute colds and screened for viruses. Results: A total of 293 adverse events occurred with Echinacea and 306 with placebo treatment. Nine and 10% of participants experienced adverse events, which were at least possibly related to the study drug (adverse drug reactions).Thus, the safety of Echinacea was noninferior to placebo. Echinacea reduced the total number of cold episodes, cumulated episode days within the group, and pain-killer medicated episodes. Echinacea inhibited virally confirmed colds and especially prevented enveloped virus infections (p < 0.05). Echinacea showed maximal effects on recurrent infections, and preventive effects increased with therapy compliance and adherence to the protocol. Conclusions: Compliant prophylactic intake of E. purpurea over a 4-month period appeared to provide a positive risk to benefit ratio (AU)

Mechanical induction of cough in Idiopathic Pulmonary Fibrosis.

BACKGROUND: Patients with idiopathic pulmonary fibrosis (IPF) frequently develop a dry, irritating cough which often proves refractory to anti-tussive therapies. The precise pathogenetic mechanisms responsible for this cough are unknown. We hypothesised that changes in nerves modulating mechanical sensitivity in areas of interstitial fibrosis might lead to enhanced cough response to mechanical stimulation of the chest in IPF. METHODS: We studied 27 non-smoking subjects with IPF (63% male), mean (SD) age 71.7 (7) years and 30 healthy non-smokers. Quality of life (Leicester Cough Questionnaire), cough symptom scores and cough severity scores (visual analog scales) were recorded. Percussion stimulation was applied over the posterior lung base, upper anterior chest and manubrium sternum at sequential frequencies (20 Hertz (Hz), 40 Hz and 60 Hz) for up to 60 seconds and repeated twice at two minute intervals. The number of subjects achieving two and five-cough responses, total cough counts and cough latency were recorded. In separate experiments, the effect of mechanical stimulation on the pattern of breathing was determined in eight IPF subjects and five control subjects. RESULTS: In patients with IPF, we demonstrated strong correlations between subjective cough measurements, particularly the cough symptom score and Leicester Cough Questionnaire (r = -0.86; p < 0.001). Mechanical percussion induced a true cough reflex in 23/27 (85%) IPF subjects, but only 5/30 (17%) controls (p < 0.001). More patients with IPF reached the two-cough response at a lower frequency (20 Hz) posteriorly than at other positions. Highest mean cough totals were seen with stimulation at or above 40 Hz. Mechanical stimulation had no effect on respiratory rate but increased tidal volume in four (50%) subjects with IPF, particularly at higher frequencies. It was associated with increased urge to cough followed by a true cough reflex. CONCLUSIONS: This study demonstrates that patients with IPF show enhanced cough reflex sensitivity to mechanical stimulation of the chest wall whilst normal individuals show little or no response. The observation that low frequency stimulation over the lung base, where fibrosis is most extensive, induces cough in more patients than at other sites supports the hypothesis that lung distortion contributes to the pathogenesis of cough in IPF.

A double-blind, randomised, crossover study of two doses of a single-tablet combination of ibuprofen/paracetamol and placebo for primary dysmenorrhoea.

OBJECTIVES: Efficacy of pain relief may potentially be enhanced by combining two or more analgesics with different mechanisms of action. The objective of this study was to assess the efficacy and tolerability of a novel single-tablet combination of ibuprofen and paracetamol compared with placebo in females experiencing moderate-to-severe pain due to primary dysmenorrhoea, a prevalent, recurrent condition characterised by pain at the time of menses. METHODS: This was a phase II/III, double-blind, randomised, cross-over, single-dose study in 94 women with moderate-to-severe dysmenorrhoea, examining the efficacy and tolerability of one or two tablets of a single-tablet combination of ibuprofen 200 mg/paracetamol 500 mg compared with placebo. CLINICAL TRIAL REGISTRATION: ISRCTN42521357 RESULTS: Total pain relief over 6 hours post-dose (TOTPAR(0-6h)) was significantly greater following administration of two tablets of the single-tablet combination of ibuprofen 200 mg/paracetamol 500 mg compared with placebo (LS means: 2.35, 1.85, respectively; p = 0.0001) and approached significance for one tablet (LS mean: 2.10; p = 0.054). Statistically superior pain relief and reductions in pain intensity were achieved from 2 hours and 90 minutes post-dose, respectively, with the higher dose combination, and from 4 hours with the lower dose combination compared with placebo. Overall effectiveness (sum of pain intensity difference and pain relief score [SPRID] over 6 hours) were statistically superior to placebo for both one and two tablets of the ibuprofen/paracetamol combination (p = 0.0011 and p = 0.03, respectively). Both dose combinations were well-tolerated. Adverse events were minor and their frequency and nature did not differ with either treatment compared with placebo. CONCLUSIONS: One or two tablets of a single-tablet combination of ibuprofen 200 mg/paracetamol 500 mg is well-tolerated and provides superior analgesic efficacy to placebo in patients with primary dysmenorrhoea.

Race and ethnicity in nasal plastic surgery: a need for science.

Race and ethnicity have no scientific or anthropologic validity, yet nasal plastic surgeons continue to categorize patient demographic variables according to racial and ethnic lines. The aim of this article is to discuss the problems of using race and ethnicity as demographic variables in nasal surgery. It is important to define the population demographics in any surgical study, but race and ethnicity are categories without any scientific basis. The nasal index or other anthropometric objective measures of the external nose may be used as discriminators of variation for studies in rhinology, but more studies are required to define their clinical relevance and usefulness in plastic surgery. The article critically examines the use of racial/ethnic categories and anthropometric measurements in nasal plastic surgery.

Effects of intranasal xylometazoline, alone or in combination with ipratropium, in patients with common cold.

BACKGROUND: Common cold is one of the most prevalent conditions that family doctors encounter. One of the first symptoms to occur is nasal congestion, which can have a negative impact on daily life and prompts many patients to seek treatment for relief. Xylometazoline nasal spray (Otrivin*) is a topical decongestant that has been used successfully for many years and is generally recognized as an effective and safe therapy. However, most studies have investigated its clinical efficacy in healthy patients and few have included patients with common cold. SCOPE: To review the published clinical efficacy and safety of xylometazoline alone and in combination in the management of nasal congestion in patients with common cold. Literature searches of PubMed and the Cochrane Library were conducted to obtain published open or blinded, randomized, placebo- or active-controlled studies on the use of xylometazoline hydrochloride for the symptomatic relief of nasal congestion in patients with common cold. Searches included papers published in English only, up to September 2009. FINDINGS: Despite the small number of studies identified in common cold (n = 4), as per search criteria defined, intranasal xylometazoline quickly and effectively relieved nasal congestion. When used alone, xylometazoline had a clinically relevant decongestant effect that was significantly superior for up to 10 hours compared with placebo. The superior decongestant effect with xylometazoline led to high patient satisfaction with treatment. When used in combination with ipratropium bromide, nasal congestion and rhinorrhoea were treated simultaneously, leading to significantly higher patient general impression scores compared with either agent used alone. Xylometazoline was well tolerated, with generally mild to moderate nasal-related side effects (e.g. epistaxis in 3.4% of patients, and blood-tinged mucus in 10-26% of patients) that were easily resolved; the most frequently reported non-nasal AEs were headache (3.4%) and period pain (10.3%); no cases of sedation were reported. As expected, no rhinitis medicamentosa or rebound congestion was noted with short-term use (<10 days). No clinically important differences in ciliary motility and mucociliary clearance were observed. Xylometazoline does not result in sympathomimetic systemic side effects seen with oral decongestants (e.g. pseudoephedrine, phenylephrine). CONCLUSIONS: The few studies available in common cold suggest that intranasal xylometazoline provides fast and effective relief of nasal congestion and is well tolerated. When xylometazoline is used in combination with ipratropium, patients with common cold experience the additive benefit of nasal congestion and rhinorrhoea being treated simultaneously.

Inferior turbinate surgery and nasal airflow: evidence-based management.

PURPOSE OF REVIEW: This review will discuss the evidence-based management of enlarged inferior turbinate by considering methods of assessing nasal airflow, controversies surrounding patient selection and surgical outcomes. RECENT FINDINGS: There is currently no consensus on patient selection for turbinate surgery. Patients are empirically offered surgery on the basis of subjective complaint of nasal obstruction and surgeon's clinical examination. Few authors have utilized objective measurements of nasal airflow such as rhinomanometry to select suitable patients for surgery. There is a small body of evidence suggesting that more robust criteria of selecting patients, using a nasal decongestant test and rhinomanometry, may have some influence on the surgical outcome. Although most surgical techniques demonstrate improvement in postoperative nasal airflow and subjective scores, it is impossible to draw conclusions as to which technique is best suited for treating inferior turbinate enlargement. The heterogeneous study cohorts, differing patient selection criteria and outcome measures used do not allow meta-analysis of outcomes and comparison between surgical techniques. SUMMARY: Inferior turbinate surgery is an evolving operative concept and the evidence supporting the efficacy of the various techniques remains undecided. More prospective controlled studies are needed with both objective and subjective outcome measures.

The nasal decongestant effect of xylometazoline in the common cold.

BACKGROUND: Xylometazoline is a nasal decongestant spray that constricts nasal blood vessels and increases nasal airflow, enabling patients with a blocked nose to breathe more easily. The purpose of this study was to characterize objectively and subjectively the decongestant and additional effects of xylometazoline in the common cold. METHODS: A double-blind, placebo-controlled, parallel group study was performed. Patients with a common cold (n = 61) were treated with xylometazoline 0.1% (n = 29) or placebo (saline solution; n = 32; 1 spray three times a day for up to 10 days). The primary objective was to determine the decongestant effect (nasal conductance); the secondary objectives were to determine the peak subjective effect (visual analog scale), duration of relief of nasal congestion, total and individual cold symptoms and general well-being (patients' daily diary), and adverse events (AEs). RESULTS: The decongestant effect of xylometazoline was significantly greater than placebo, as shown by the nasal conductance at 1 hour (384.23 versus 226.42 cm(3)/s; p