Respiratory viruses and cot death.

Respiratory viruses and histological appearances of the lung were studied prospectively in an unselected series of 104 children who died between 1 week and 2 years of age. Thirty-one of the cases were cot deaths. Seven of these showed evidence of active virus infection in the lower respiratory tract. Similar evidence was found in two children who died from known causes and did not have a severe respiratory illness terminally. Although in some cases of cot death respiratory viruses may be responsible for a severe and rapidly overwhelming illness, the present results are compatible with an alternative hypothesis-namely, that minor respiratory illness may trigger sudden apnoea.     

Respiratory viruses and sudden infant death.

Viruses were shown to be present in the respiratory tract in 200 of 763 cases of the sudden infant death syndrome studied in the nine years 1974-82. Epidemiological and pathological evidence suggested that the distribution of viruses in the sudden infant death syndrome differs between infants aged 3 months or less and those aged over 3 months: the incidence of detection of virus was 14% in the younger group compared with 39% in the older group. The distribution of the viruses in these two groups was compared with that in 1341 live infants with respiratory virus infections. Adenovirus, influenza virus, parainfluenza virus, and rhinovirus had similar distribution among the victims of the sudden infant death syndrome and live controls. The incidence of detection of respiratory syncytial virus was increased in the older infants dying of the sudden infant death syndrome (90% of the cases detected) compared with the older group of live infants (53%). Antibody studies, detection of virus, and epidemiological data suggest that respiratory syncytial virus may be a precipitating factor of sudden death in older infants.     

Identification and management of adults with asthma prone to exacerbations: can we do better?

Exacerbations are a major cause of morbidity in asthma and generate high health costs. Identification and management of adults with asthma who are prone to exacerbations is of considerable importance as by this means it should be possible to reduce the number of patients who currently experience inadequately controlled disease. Exacerbations occur most frequently in individuals with severe disease. Other risk factors include a history of a recent exacerbation, co-morbidities such as a raised body mass index and psychological problems as well as current smoking and lower socio-economic status. A low FEV₁, particularly if combined with the additional information from questionnaires helps predict exacerbations. Despite the association between these risk factors and exacerbations it remains difficult to accurately predict in an individual patient with asthma whether they will go on to develop an exacerbation in the future. A major aim of international guidelines on the management of asthma is to prevent future risks of exacerbations, but some patients, particularly those with severe disease, respond poorly to current therapies and continue to experience recurrent exacerbations. There is an unmet need for improved management strategies and drugs targeted at preventing asthma exacerbations. Monitoring induced sputum eosinophil cell counts is helpful in preventing exacerbations in some patient with severe asthma. Future developments are likely to include the identification of better biomarkers to predict exacerbations or the cause of exacerbations, augmentation of the immunological response to viruses at the time of the exacerbation, the use of telemonitoring in patients with severe asthma and the development of improved therapies targeted at reducing exacerbations.     

Role of deficient type III interferon-lambda production in asthma exacerbations

Rhinoviruses are the major cause of asthma exacerbations, and asthmatics have increased susceptibility to rhinovirus and risk of invasive bacterial infections. Here we show deficient induction of interferon-lambdas by rhinovirus in asthmatic primary bronchial epithelial cells and alveolar macrophages, which was highly correlated with severity of rhinovirus-induced asthma exacerbation and virus load in experimentally infected human volunteers. Induction by lipopolysaccharide in asthmatic macrophages was also deficient and correlated with exacerbation severity. These results identify previously unknown mechanisms of susceptibility to infection in asthma and suggest new approaches to prevention and/or treatment of asthma exacerbations.     

Respiratory infections precede adult-onset asthma

Background

Respiratory infections in early life are associated with an increased risk of developing asthma but there is little evidence on the role of infections for onset of asthma in adults. The objective of this study was to assess the relation of the occurrence of respiratory infections in the past 12 months to adult-onset asthma in a population-based incident case-control study of adults 21–63 years of age.

Methods/PrincipalFindings

We recruited all new clinically diagnosed cases of asthma (n = 521) during a 2.5-year study period and randomly selected controls (n = 932) in a geographically defined area in South Finland. Information on respiratory infections was collected by a self-administered questionnaire. The diagnosis of asthma was based on symptoms and reversible airflow obstruction in lung function measurements. The risk of asthma onset was strongly increased in subjects who had experienced in the preceding 12 months lower respiratory tract infections (including acute bronchitis and pneumonia) with an adjusted odds ratio (OR) 7.18 (95% confidence interval [CI] 5.16–9.99), or upper respiratory tract infections (including common cold, sinusitis, tonsillitis, and otitis media) with an adjusted OR 2.26 (95% CI 1.72–2.97). Individuals with personal atopy and/or parental atopy were more susceptible to the effects of respiratory infections on asthma onset than non-atopic persons.

Conclusions/Significance

This study provides new evidence that recently experienced respiratory infections are a strong determinant for adult-onset asthma. Reducing such infections might prevent onset of asthma in adulthood, especially in individuals with atopy or hereditary propensity to it.     

Use of mechanical ventilation in adults with severe asthma.

Asthma severe enough to require intubation and mechanical ventilation is associated with a mortality rate of about 10%. Therapeutic modalities are ever-changing and at times controversial. This paper provides an update on such modalities and presents, in a step-wise fashion, those most appropriate for practical patient care. The timing of intubation and the methods used to control airway patency, arterial pH and gas levels, and hemodynamic status are crucial to the success of therapy. Finally, conventional and disputed methods of bronchodilation are outlined.     

Prevalence of asthma in adults in Busselton,Western Australia.

OBJECTIVE--To estimate whether the prevalence of asthma in adults increased over a nine year interval. DESIGN--Serial cross sectional studies of the population with a protocol that included both subjective and objective measurements. SETTING--Busselton, Western Australia. SUBJECTS--A random sample of 553 subjects aged 18-55 years in 1981, and of 1028 subjects aged 18-55 years in 1990. MAIN OUTCOME MEASURES--Respiratory symptoms measured by self administered questionnaire, bronchial responsiveness measured by bronchial challenge with histamine, and allergy measured by skin prick tests. RESULTS--Symptoms with increased prevalence were those with significant association with allergy in this population. Recent wheeze increased from 17.5% to 28.8% (p < 0.001) and diagnosed asthma increased from 9.0% to 16.3% (p < 0.001). The increase was greatest in subjects less than 30 years old. The prevalence of shortness of breath coming on at rest and of hay fever also increased significantly, but the prevalence of shortness of breath on exertion, chronic cough, bronchial hyperresponsiveness, current asthma (defined as recent wheeze plus bronchial hyperresponsiveness), and allergy did not increase. The severity of bronchial responsiveness did not change significantly in any symptom group. CONCLUSIONS--Young adults showed a significant increase in reporting of symptoms related to allergy but not in the prevalence of current asthma. The increase in symptoms may be due to increased awareness of asthma in this community, to changed treatment patterns, or to increased exposures to allergens.     

Validity of the common cold questionnaire (CCQ) in asthma exacerbations

Background

The common cold questionnaire (CCQ) is used to discriminate those with and without a viral infection. Its usefulness in people with acute asthma is unknown. Our aim was to assess the ability of the CCQ to detect viral infection and to monitor recovery during a viral induced asthma exacerbation and confirmed by virological testing.

Methodology/Principal Findings

We studied subjects (≥7 yrs) admitted to hospital with acute asthma and diagnosed as positive (n = 63), or negative to viral infection (n = 27) according to molecular and virological testing from respiratory samples. CCQ, asthma history and asthma control questionnaires were completed and repeated 4–6 weeks later. Sensitivity, specificity, and response to change of the CCQ were assessed by receiver operator curve (ROC) analysis and effect size calculation respectively. The CCQ did not discriminate between viral and non-viral infection for subjects with asthma (sensitivity = 76.2%; specificity = 29.6%). ROC analysis could not differentiate between positive or negative virus in subjects with asthma. The CCQ had a large response to change following recovery (effect size = 1.01). 39% of subjects recovering from viral exacerbation remained positive to virological testing at follow-up despite improvement in clinical symptoms. The CCQ reflected clinical improvement in these subjects, thus providing additional information to complement virological testing.

Conclusions/Significance

The CCQ is a useful instrument for monitoring response to viral infection in people with asthma. Reliable differentiation between viral and non-viral asthma exacerbations was not achieved with the CCQ and requires specific virological testing. When combined with virological testing, the CCQ should be a useful outcome measure for evaluating therapies in viral-induced asthma.     

Overdiagnosis of asthma in obese and nonobese adults

Background

It is unclear whether asthma is overdiagnosed in developed countries, particularly among obese individuals, who may be more likely than nonobese people to experience dyspnea.

Methods

We conducted a longitudinal study involving nonobese (body mass index 20–25) and obese (body mass index ≥ 30) individuals with asthma that had been diagnosed by a physician. Participants were recruited from 8 Canadian cities by means of random-digit dialing. A diagnosis of current asthma was excluded in those who did not have evidence of acute worsening of asthma symptoms, reversible airflow obstruction or bronchial hyperresponsiveness, despite being weaned off asthma medications. We stopped asthma medications in those in whom a diagnosis of asthma was excluded and assessed their clinical outcomes over 6 months.

Results

Of 540 individuals with physician-diagnosed asthma who participated in the study, 496 (242 obese and 254 nonobese) could be conclusively assessed for a diagnosis of asthma. Asthma was ultimately excluded in 31.8% (95% confidence interval [CI] 26.3%–37.9%) in the obese group and in 28.7% (95% CI 23.5%–34.6%) in the nonobese group. Overdiagnosis of asthma was no more likely to occur among obese individuals than among nonobese individuals (p = 0.46). Of those in whom asthma was excluded, 65.5% did not need to take asthma medication or seek health care services because of asthma symptoms during a 6-month follow-up period.

Interpretation

About one-third of obese and nonobese individuals with physician-diagnosed asthma did not have asthma when objectively assessed. This finding suggests that, in developed countries such as Canada, asthma is overdiagnosed.Between 1980 and 1994, the age-adjusted prevalence of asthma increased by 75% in Canada and the United States.^1,2 The prevalence of both the symptoms and diagnosis of asthma may depend heavily on an awareness of asthma in the population studied.³ In recent decades, awareness of asthma has increased significantly among patients and their physicians. Part of this awareness has been stimulated by the medical community and part by the pharmaceutical industry, which has developed new medications for asthma and has directly or indirectly advertised these medications to patients and health care providers.³ In Scotland, the proportion of children reporting asthma symptoms who received a diagnosis of asthma from their physicians increased from 28% in 1964 to 64% in 1999.⁴ Part of the increase in prevalence may be attributable to changes in diagnostic labelling.Over the past 3 decades, the incidence and prevalence of obesity has increased concurrently with the incidence and prevalence of asthma, which indicates a possible link between obesity and asthma.^5–7 Studies have suggested that asthma is almost twice as likely to be diagnosed in obese people as in nonobese people. In Canada and the United States, 8.8%–9.2% of obese adults reported having received a diagnosis of asthma from a physician, as compared with 4%–5% of nonobese adults.^8,9It is unclear whether this increased tendency to diagnose asthma in patients with respiratory symptoms is appropriate, or whether asthma may be overdiagnosed in developed countries. Potential overdiagnosis of asthma may be even more pronounced among obese people. Obesity decreases chest wall compliance, which results in reduced lung volumes, increased work of breathing and increased energy and oxygen costs of breathing.^10–12 Because obese patients report more dyspnea and asthma-like symptoms than nonobese patients, they may be more likely to be misdiagnosed by their physicians as having asthma.We conducted this study to determine the proportion of obese and nonobese Canadian adults who have an incorrect diagnosis of asthma. We also assessed whether overdiagnosis of asthma was more prevalent among obese than among nonobese individuals. Finally, we determined what proportion of obese and nonobese patients could safely discontinue their asthma medications once a diagnosis of asthma was excluded.     

The role of IL-15 deficiency in the pathogenesis of virus-induced asthma exacerbations

Rhinovirus infections are the major cause of asthma exacerbations. We hypothesised that IL-15, a cytokine implicated in innate and acquired antiviral immunity, may be deficient in asthma and important in the pathogenesis of asthma exacerbations. We investigated regulation of IL-15 induction by rhinovirus in human macrophages in vitro, IL-15 levels in bronchoalveolar lavage (BAL) fluid and IL-15 induction by rhinovirus in BAL macrophages from asthmatic and control subjects, and related these to outcomes of infection in vivo. Rhinovirus induced IL-15 in macrophages was replication-, NF-κB- and α/β interferon-dependent. BAL macrophage IL-15 induction by rhinovirus was impaired in asthmatics and inversely related to lower respiratory symptom severity during experimental rhinovirus infection. IL-15 levels in BAL fluid were also decreased in asthmatics and inversely related with airway hyperresponsiveness and with virus load during in vivo rhinovirus infection. Deficient IL-15 production in asthma may be important in the pathogenesis of asthma exacerbations.     

Community study of role of viral infections in exacerbations of asthma in 9-11 year old children.

OBJECTIVE--To study the association between upper and lower respiratory viral infections and acute exacerbations of asthma in schoolchildren in the community. DESIGN--Community based 13 month longitudinal study using diary card respiratory symptom and peak expiratory flow monitoring to allow early sampling for viruses. SUBJECTS--108 Children aged 9-11 years who had reported wheeze or cough, or both, in a questionnaire. SETTING--Southampton and surrounding community. MAIN OUTCOME MEASURES--Upper and lower respiratory viral infections detected by polymerase chain reaction or conventional methods, reported exacerbations of asthma, computer identified episodes of respiratory tract symptoms or peak flow reductions. RESULTS--Viruses were detected in 80% of reported episodes of reduced peak expiratory flow, 80% of reported episodes of wheeze, and in 85% of reported episodes of upper respiratory symptoms, cough, wheeze, and a fall in peak expiratory flow. The median duration of reported falls in peak expiratory flow was 14 days, and the median maximum fall in peak expiratory flow was 81 l/min. The most commonly identified virus type was rhinovirus. CONCLUSIONS--This study supports the hypothesis that upper respiratory viral infections are associated with 80-85% of asthma exacerbations in school age children.