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PubMed2024

Rhinovirus infection of airway epithelial cells uncovers the non-ciliated subset as a likely driver of genetic susceptibility to childhood-onset asthma.

Asthma is a complex disease caused by genetic and environmental factors. Epidemiological studies have shown that in children, wheezing during rhinovirus infection (a cause of the common cold) is associated with asthma development during childhood. This has led scientists to hypothesize there could be a causal relationship between rhinovirus infection and asthma or that RV-induced wheezing identifies individuals at increased risk for asthma development. However, not all children who wheeze when they have a cold develop asthma. Genome-wide association studies (GWAS) have identified hundreds of genetic variants contributing to asthma susceptibility, with the vast majority of likely causal variants being non-coding. Integrative analyses with transcriptomic and epigenomic datasets have indicated that T cells drive asthma risk, which has been supported by mouse studies. However, the datasets ascertained in these integrative analyses lack airway epithelial cells. Furthermore, large-scale transcriptomic T cell studies have not identified the regulatory effects of most non-coding risk variants in asthma GWAS, indicating there could be additional cell types harboring these "missing regulatory effects". Given that airway epithelial cells are the first line of defense against rhinovirus, we hypothesized they could be mediators of genetic susceptibility to asthma. Here we integrate GWAS data with transcriptomic datasets of airway epithelial cells subject to stimuli that could induce activation states relevant to asthma. We demonstrate that epithelial cultures infected with rhinovirus significantly upregulate childhood-onset asthma-associated genes. We show that this upregulation occurs specifically in non-ciliated epithelial cells. This enrichment for genes in asthma risk loci, or 'asthma heritability enrichment' is also significant for epithelial genes upregulated with influenza infection, but not with SARS-CoV-2 infection or cytokine activation. Additionally, cells from patients with asthma showed a stronger heritability enrichment compared to cells from healthy individuals. Overall, our results suggest that rhinovirus infection is an environmental factor that interacts with genetic risk factors through non-ciliated airway epithelial cells to drive childhood-onset asthma.

Preprint↗
PubMed2006

Substitution of phenylephrine for pseudoephedrine as a nasal decongeststant. An illogical way to control methamphetamine abuse.

The aim of this review was to investigate the rationale for replacing the nasal decongestant pseudoephedrine (PDE) with phenylephrine (PE) as a means of controlling the illicit production of methamphetamine. A literature search was conducted in electronic databases and use of textbooks. Restrictions have been placed on the sale of PDE in the USA in an attempt to control the illicit production of methamphetamine. This has caused a switch from PDE to PE in many common cold and cough medicines. PE is a poor substitute for PDE as an orally administered decongestant as it is extensively metabolized in the gut and its efficacy as a decongestant is unproven. Both PDE and PE have a good safety record, but the efficacy of PDE as a nasal decongestant is supported by clinical trials. Studies in the USA indicate that restricting the sale of PDE to the public as a medicine has had little impact on the morbidity and number of arrests associated with methamphetamine abuse. Restricting the sale of PDE in order to control the illicit production of methamphetamine will deprive the public of a safe and effective nasal decongestant and force the pharmaceutical industry to replace PDE with PE, which may be an ineffective decongestant. Restrictions on sales of PDE to the public may not reduce the problems associated with methamphetamine abuse.

Amphetamine-Related Disorders↗
PubMed1992

Viruses as precipitants of asthma symptoms. II. Physiology and mechanisms.

The upper and lower airways have complimentary roles in the ultimate object of supplying the body with oxygen whilst removing waste products of metabolism. Pathology in one area may trigger a response in another, the physiology of which, in the case of virus-induced asthma exacerbations remains poorly characterized. Viral infection of the upper airways by common cold viruses frequently triggers a response in the lower airways leading to prolonged morbidity, especially in subjects with significant pre-existing airway disease. The induction or amplification of BHR may be an important mechanism whereby asthmatic symptoms are produced although the cellular and tissue events or reflex mechanisms activated by viral illnesses and underlying BHR changes are poorly defined and may be dependent on the type and the severity of infection. Children and asthmatics tend to develop frequent colds setting in motion a sequence of events culminating in airway obstruction and symptoms of wheezing, coughing and chest tightness. This may reflect independent inflammatory changes caused by a simply additive effect of viral damage to the mucosa superimposed upon pre-existing allergic inflammation (Fig. 1). Few if any symptoms will develop in normal subjects with a mild cold whereas significant symptoms may ensue if the cold is severe and induces marked lower airway swelling, secretions and smooth muscle contraction; pathology to which children who have small calibre airways may be particularly susceptible. In asthmatics even a mild cold frequently induces exacerbation of symptoms, while serious life-threatening asthma attacks may occur associated with a severe cold. Some studies have suggested that this effect is not only additive but also synergistic and brought about by release of the mediators already present in increased quantities, the induction of IgE synthesis, or by the potentiation of neural and epithelial damage. The combined effect of both asthma and viruses may thus be amplified and result in a sustained and refractory period of airway obstruction, severe symptoms and unstable asthma. As most hospital admissions for asthma occur over the winter months and soon after the start of the school terms [115], spread of viruses through the community to susceptible individuals may be the single most important cause of sustained exacerbations of asthma. Definition of the pathological and physiological mechanisms involved will lead to better understanding and may thus provide a basis for prevention and the development of effective forms of treatment for virus-induced asthma.

Airway Obstruction↗
PubMed1982

Rhinitis, sinusitis and otitis media in Kartagener's syndrome (primary ciliary dyskinesia).

Ear, nose and throat symptoms and signs were studied in 15 patients with Kartagener's syndrome: a triad consisting of chronic rhinosinusitis, chronic bronchitis with bronchiectasis, and situs inversus. The triad is caused by primary ciliary dyskinesia and characterized by absent or considerably reduced mucociliary transport. Daily accumulation of secretions in the nose, chronic recurrent secretory otitis media and sinusitis occurred in all subjects. Characteristically, nasal discharge started at birth or was first detected in early childhood. Apparently, the frequency of common colds and of acute purulent otitis media was not increased. As primary ciliary dyskinesia can occur without situs inversus, knowledge of the typical ENT symptoms is essential for making an early diagnosis, which is important for the correct management of the disease. While a conservative surgical approach to treatment of the ENT symptoms is recommended, early and active treatment of the bronchial symptoms is probably important for prevention of further lung damage and development of bronchiectasis.

Adolescent↗
PubMed1988

What anatomy shall we teach medical and dental students in a primary health care curriculum?

The opinions of 142 doctors on the relevance of anatomy to the diagnosis and management of common clinical problems in their current medical and dental practice were analysed. This was in a bid to determine the relevant anatomy course content for the new primary health care oriented medical and dental curriculum of the College of Medicine, University of Lagos. The respondents gave high scores to the relevance of anatomy knowledge to the management of acute abdomen (mean = 3.5), dislocated shoulder (3.3), Colles' fracture (3.2), palmar space abscess (3.2), obstructed labour (3.2), carcinoma of the breast (3.2), ectopic pregnancy (3.1), flail chest (3.1) and upper respiratory obstruction (3.0). They gave minimal scores to helminthiasis (mean = 1.5) common cold and anaemia (1.6), sickle cell disease (1.7), gastroenteritis (1.8), dental abscess (2.0), hypertension (2.2) and asthma (2.2). A basis for selecting relevant anatomy course content is deduced for an undergraduate curriculum in which the responsibilities and competence of the graduates is known. A nationwide extension of the study, especially amongst general practitioners and first-line doctors in rural areas, would be useful for identification of health problems that require little or no knowledge of anatomy and which can be safely managed by lower cadres of health personnel, traditional practitioners and members of the lay community.

Anatomy↗
PubMed1985

Effects of killed and live attenuated influenza vaccine on symptoms and specific airway conductance in asthmatics and healthy subjects.

Killed and live influenza virus vaccines were given to asthmatics and healthy subjects to investigate symptoms and alterations in their respiratory performance after vaccination. Polyvalent killed influenza virus vaccine was given to 16 asthmatics and live attenuated influenza virus vaccine to 23 asthmatics and 21 healthy subjects. Fourteen of the 16 asthmatics vaccinated with the killed vaccine displayed a significant rise in serum antibody level as measured by a single radial haemolysis in gel (SRH test). 11 of the 23 asthmatics and 14 of the 21 healthy subjects vaccinated with the live attenuated vaccine displayed a significant rise in the SRH test. Among the subjects with no measurable initial antibodies and with a significant rise in the SRH test, one asthmatic vaccinated with the killed vaccine experienced symptoms of common cold with fever and dyspnoea 1 week after vaccination. Three asthmatics and four healthy subjects vaccinated with live attenuated vaccine experienced mild symptoms, mainly rhinorrhoea, cough and sore throat 2 to 3 days after vaccination. No alterations in specific airway conductance in asthmatics or in healthy subjects were observed. We conclude that both killed and live attenuated influenza virus vaccines are tolerated well by asthmatics and appear to be safe for asthma patients.

Adult↗
PubMed1995

Prevalence of asthma and asthma symptoms in a general population sample from northern Italy. European Community Respiratory Health Survey--Italy.

The European Community Respiratory Health Survey is an international survey of the general population which aims to establish whether there are significant variations in the prevalence of asthma among European countries. The present paper reports the prevalence of asthma and asthma-like symptoms in a sample of subjects living in three areas of northern Italy: Turin, Pavia, and Verona. Samples of residents 20-44 years old (3000 subjects in Turin and Verona and 1000 in Pavia) stratified by sex (M:F = 1/1) were randomly selected from local health authority lists in the three participating areas. To correct the observed prevalence estimate for nonresponse bias, a method proposed by Drane was applied. Of the sampled subjects, 86% (6031) participated in the survey. Two different definitions of asthma were adopted: 1) prevalence of asthma attack in the last 12 months; 2) prevalence of asthma attack or treatment with antiasthmatic drugs, or both wheezing apart from the common cold and wheezing with shortness of breath. This combination of symptoms has been called current asthma. According to these definitions, the prevalence of asthma attack was 3.47% (3.74% in men and 3.14% in women), and the prevalence of current asthma was 5.01% (5.07% in men and 4.90% in women). The lowest prevalence was found in Pavia; the highest in Turin. Our findings support the hypothesis that the difference in prevalence reflects the difference in mortality.

Adult↗
PubMed1998

Improvement with disodium cromoglycate of neutrophil phagocytosis and respiratory burst activity in a patient with hyperimmunoglobulin E syndrome.

We report a case of hyperimmunoglobulin E syndrome (HIE) complicated by neutrophil deficiency which was successfully treated with oral administration of disodium cromoglycate. A 48-year-old Japanese man with HIE developed Streptococcus pneumoniae meningitis. Laboratory tests after the meningitis revealed persistent neutropenia (300-800/mm3) and defects of phagocytosis and bacterial killing by neutrophils. Administration of disodium cromoglycate was started, and neutrophil counts gradually increased to 1200-1600/mm3. The impaired neutrophil activities returned to normal. The patient improved clinically; during the 2-year treatment, he had only two brief episodes of the common cold. Disodium cromoglycate may have potential clinical use in the treatment of cases of HIE even with neutrophil deficiency.

Cromolyn Sodium↗
PubMed2006

Soluble CD14 at 2 yr of age: gender-related effects of tobacco smoke exposure, recurrent infections and atopic diseases.

The endotoxin receptor soluble CD14 (sCD14) has been implicated in the 'hygiene hypothesis' suggesting reduced allergic sensitization with bacterial stimulation. However, the relationship between early life sCD14 and allergic diseases is conflicting. We aimed to investigate whether possible risk factors for allergic diseases were associated with sCD14 levels at 2 yr of age. In the nested case-control study of the birth cohort studies 'Environment and Childhood Asthma study in Oslo' 411 children selected with recurrent bronchial obstruction (rBO) (n=241) and no bronchial obstruction (n=170) by 2 yr were investigated with skin prick test and structured parental interview at age 2 yr. Exposure to tobacco smoke, pets and infections was recorded semi-annually by questionnaires (0-2 yr). The sCD14 was analysed from frozen, stored serum by ELISA technique. Regression analyses were performed in all subjects with complete data (n=406, 180 girls), and in girls and in boys separately. Mean sCD14 (ng/ml) was significantly higher among girls 2035 (1973-2096) vs. 1947 (1890-2004) (boys). The sCD14 was significantly reduced among girls exposed to antenatal maternal smoking and with parental asthma, after adjusting for age, parental rhino-conjunctivitis, pet keeping and childhood infections. Recurrent otitis media (OM) increased and common colds significantly decreased sCD14 levels in girls. Boys with atopic dermatitis and rBO had reduced sCD14. Pet exposure was not significantly associated with sCD14. We report novel gender-related effects of sCD14 in early life and suggest that gender, tobacco smoke exposure, age and middle ear disease in particular should be accounted for when assessing the role of sCD14 in childhood allergic diseases.

Age Factors↗
PubMed2005

Case-control study of medical history and idiopathic pulmonary fibrosis in Japan.

OBJECTIVES: A few epidemiological studies have indicated that a patient's past medical history may contribute to the risk of developing idiopathic pulmonary fibrosis (IPF). A relationship between a history of selected disorders and the risk of IPF was assessed in a multicentre hospital-based case-control study in Japan. METHODOLOGY: Included in the study were 104 patients of IPF, aged 40 years or over, who had been diagnosed within the previous 2 years, in accordance with the most recent criteria. Control subjects, aged 40 years or over, consisted of 56 hospitalized patients diagnosed as having acute bacterial pneumonia and four outpatients with the common cold. Adjustment was made for age, gender, region, pack-years of smoking, employment status, occupational exposure and BMI. RESULTS: Medical histories of hypertension, hyperlipidaemia, coronary heart disease, diabetes mellitus, hepatitis C virus infection, tuberculosis, asthma, atopic dermatitis and allergic rhinitis were not statistically significantly associated with the risk of IPF, although cases were more likely to have suffered from allergic rhinitis and less likely to have been asthmatics than control subjects. Having a child with a history of allergic rhinitis, but not of asthma or atopic dermatitis, was significantly related to an increased risk of IPF. CONCLUSIONS: These findings suggest that a genetic predisposition to allergic rhinitis may be associated with an increased risk of IPF.

Aged↗
PubMed1989

Inherited deficiency of the seventh component of complement: studies of C7-consuming activity.

Neither the hemolytic activity nor the protein level of the seventh component of serum complement (C7) was detectable in an 8-year-old girl with nephritis, but in her parents and her brother, they were about half of the normal level. The patient was a homozygote type with a complete deficiency of C7 while her parents and brother were all heterozygote type with a partial deficiency of C7. C7-consuming activity was demonstrated in the native serum of the patient with complete C7 deficiency, and it was found that large amounts of C56 were readily generated upon incubation of the patient's serum with zymosan. It is proposed that the C7-consuming activity in the native serum of this patient is due to small amounts of C56 generated during the activation of serum complement by some kind of infection such as a common cold.

Child↗
PubMed2005

Herpes simplex esophagitis in the immunocompetent host.

We report here a case of herpes esophagitis with Mallory-Weiss syndrome in an immunocompetent host. A 26-year-old man was admitted to our hospital because of common cold symptoms and eruptions on the body. On day 2 after hospitalization, the patient showed high-grade fever, odynophagia and hematemesis. Upper gastrointestinal endoscopic examination showed multiple ulcerations throughout the mid- and distal esophagus. Bleeding from a Mallory-Weiss tear was also seen. Follow-up endoscopic examinations showed whitish exudates on day 5. Histological examination of biopsy specimens showed Cowdry type A intranuclear inclusion bodies in epithelial cells. Positive staining of a specific antibody against herpes simplex virus-1 (HSV-1) was seen in the nuclei of esophageal epithelial cells. Primary HSV-1 infection was suspected because ELISA titers of serum IgM antibody against HSV-1 were high and titers of serum IgG antibody against HSV-1 increased from an almost cut-off ratio. A diagnosis of herpes esophagitis in an immunocompetent host was made. Our case is the first report of herpes esophagitis with Mallory-Weiss syndrome in the immunocompetent host. It is important to remind herpes esophagitis in cases of severe odynophagia even in immunocompetent hosts.

Adult↗
PubMed2004

Vaccination for asthma exacerbations.

Most asthma exacerbations are caused by common cold virus infections, predominantly rhinovirus infections. Full protection against repeat infections with the same rhinovirus serotype is given by serum neutralizing antibody, but cross-reactive antibody developed against other serotypes could yield partial protection and result in attenuated cold and airway symptoms. It is proposed that vaccine-mediated induction of cross-reactive antibody might not prevent rhinovirus infections but might reduce severe asthma symptoms and exacerbations.

Asthma↗
PubMed1998

Parental smoking and respiratory illnesses in Australian children aged 0-4 years: ABS 1989-90 National Health Survey results.

OBJECTIVE: This study investigated the associations between parental smoking and respiratory infections in Australian children aged 0-4 years. METHODS: Data from the ABS 1989-90 National Health Survey were used. The exposure variables examined were maternal, paternal and combined family smoking. Outcome variables were parent-reported chronic or recent asthma, asthma wheeze, bronchitis, influenza, common cold, cough, otitis media and other respiratory conditions. Logistic regression techniques were used to control for confounding by socio-economic status, child's sex, maternal education, place of residence, ethnicity and family size. RESULTS: Of the 4,281 children in the sample, 45% lived in households with one or more current smokers and 29% had a mother who smoked. Maternal (but not paternal) smoking was significantly associated with asthma (OR 1.52, 95% CI 1.19-1.94) and asthma wheeze (OR 1.51, 95% CI 1.26-1.80). No other significant associations were observed. Positive and significant dose response relationships were found between the amount of maternal smoking and both asthma variables. Population attributable risks were calculated and almost 13% of asthma and asthma wheeze in 0-4 year old Australian children in 1989-90 was estimated to be due to maternal smoking. CONCLUSION: Large numbers of Australian children live in households with smokers. This study, like others, has shown an association between maternal smoking and respiratory illnesses in young children. Further strategies are needed to prevent or reduce young children's exposure to environmental tobacco smoke in their homes.

Asthma↗
PubMed2001

Asking the right questions of disadvantaged and homeless communities: the role of housing, patterns of illness and reporting behaviours in the measurement of health status.

OBJECTIVE: To assess the self-reported health status and its relationship to key demographic variables among patrons of a charity-run meals service at The Exodus Foundation, in urban Sydney, Australia. METHOD: Random-sample cross-sectional study of 100 face-to-face interviews (79% recruitment rate). Self-reported health status was measured by subjective rating scale, open-ended and checklist questions about presence and type of acute and chronic disease. Anaysis by logistic regression of fair-poor health status on demographic variables in Exodus patrons and genera Sydney population adjusted for age and sex using the 1995 National Health Survey. RESULTS: Compared to housed but poor counterparts within the Exodus sample, homeless people were significantly more likely to report fair-poor health status (age-adjusted OR-3.0, 95% CI 1.3-7.1). Exodus patrons, as a whole, were much more likely than Sydney's general population to report fair-poor health status, after adjusting for age and sex (OR-4.5, 95% CI 2.9-7.0) and had a more serious pattern of illness (diseases of the digestive system; depression; common cold; bronchitis; refractive errors; drug and alcohol dependence; diabetes mellitus Type II). Exodus patrons reported fewer acute and chronic illnesses with open-ended questions than with a checklist (p<0.001). CONCLUSION: In this population there was a strong relationship between poor health and homelessness. When patterns of illness and injury were measured within this disadvantaged group, they showed more serious illness types than in the general population. Such patterns may not be identified by methods often used in traditional population health surveys.

Adolescent↗
PubMed1988

Density dependence of expiratory flow--a useful basis for lung function tests?

The aim of this investigation was to study the density dependence of forced expiratory flow and the ability of tests based on density dependence to disclose smoking-induced small airways dysfunction. The lung function of 212 systematically sampled men (mean age 40.3; range 30-48 years) was studied by recording flow-volume curves during air or helium-oxygen (HeOx) breathing and by the single breath N2-test. Density dependence was expressed as the percentage increase in flow from air to HeOx when 50 and when 25% of the vital capacity (VC) remained to be expelled (dMEF50 and dMEF25). The mean dMEF50 in 59 healthy non-smokers was 40% (range +7 to +72) and the mean dMEF25 24% (range -20 to +63). Density dependence apparently decreased with relative lung volume and also with increasing age. Despite the wide variation of density dependence in the reference group, dMEF50 was on average significantly reduced in smokers, and dMEF25 in ex-smokers and subjects with symptoms such as cough and/or sputum production, wheezing unrelated to common colds and dyspnea when walking on level ground. However, only 8% of the smokers exhibited 'abnormal' density dependence (dMEF25 less than (predicted value--2RSD] as compared to 11 and 33% for the forced expiratory volume in one second (FEV1) and dN2 (alveolar slope). If abnormal dN2 in the smoking group is taken to indicate smoking-induced small airway dysfunction, then the ability of dMEF50 and dMEF25 to disclose such dysfunction is limited.

Adult↗
PubMed1987

Recurrent herpes labialis in a military brass band.

80-90% of the adult population is known to have neutralizing antibodies to herpes simplex virus type 1 (HSV1), of these 18-32% suffer from occasional recurrent herpes labialis (RHL). It is thought that local trigger factors as external traumata, UV-light and chemical stimuli, or systemic factors like fever or common cold, may induce RHL. The aim of the present study was to investigate the frequency of RHL in a military brass band and compare this with the frequency of the disease in a control population of soldiers from the same unit. Both populations were national servicemen aged 19-22 yr. The diagnosis of RHL was based on the presence of herpetic vesicles in the labial region. Of the diagnosed cases, 10% were confirmed by laboratory procedures according to standard methods. The incidence of RHL over a period of 8 months was twice as frequent in the group of brass and woodwind players as in the control group of soldiers from the same military unit. This may indicate that the mechanical trauma to the labial tissue which occurs during playing may cause the increased frequency of RHL in musicians.

Adult↗
PubMed1987

A prospective study of respiratory infections in 12-year-old children actively engaged in sports.

Data on the incidence of respiratory tract infections, antimicrobial treatment, days with fever and absence from school on account of these infections were studied in children participating in extracurricular sports activities with regular supervised training and competitive events. Swimmers, ice-hockey players and apparatus gymnasts were compared to a control group of children. Their mean age was 12.7 years at the end of the one year study. The children were examined three times during the year. More information was collected by a nurse who contacted the mothers of the children every two months. The girls had contracted more respiratory tract infections than the boys during the study. This difference was only seen regarding common colds, not regarding major bacterial respiratory infections, i.e. otitis media, tonsillitis, sinusitis and pneumonia. Because of this difference the results were analysed separately for the sexes. No differences between the sports and the control groups were seen in any respect regarding respiratory infections. Contrary to general opinion, sports participation does not seem to have a preventive effect on the occurrence of respiratory infections in children.

Adolescent↗