Characteristics of patients with seasonal allergic rhinitis and concomitant asthma.

Harris AG.

Montpellier University/INSERM, Montpellier, France. bousquet montp.inserm.fr

BACKGROUND: Allergic rhinitis and asthma often co-exist and appear to produce a continuum of airway disease, but whether the clinical characteristics of asthma in patients with seasonal rhinitis differ from those of persistent asthma has not been examined. OBJECTIVE: The aim of this retrospective study was to characterize the clinical features of patients with seasonal allergic rhinitis with concomitant asthma and to compare them with those in patients with persistent asthma. METHODS: The patient populations for this study were derived from nine prospective, placebo-controlled planned clinical trials of similar design. Six studies (958 patients) enrolled patients with seasonal allergic rhinitis and concomitant asthma; three (607 patients) involved patients with persistent asthma. In all studies, patients were excluded from oral corticosteroid therapy in the preceding 3 months, and from inhaled corticosteroids in the preceding month. RESULTS: Patients with seasonal rhinitis and asthma had a significantly (P<0.001) higher total asthma symptom score than those with persistent asthma. In particular, cough was three times more severe. The need for beta(2)-agonist as a rescue medication and the ratio of forced expiratory volume in 1 s/forced vital capacity (FVC) were similar in the two groups whereas forced expiratory fraction 25-75%/FVC was significantly (P<0.02) reduced in the persistent asthmatics. Asthma and nasal symptom severity scores were correlated in patients with seasonal rhinitis and asthma (P<0.0001). CONCLUSIONS: Patients with seasonal allergic rhinitis and concomitant asthma appear to differ from those with persistent asthma. A prospective study should be designed to discover whether patients with seasonal rhinitis and asthma may represent a distinct nosological entity, 'allergic airway disease'.

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Assessment of variations in control of asthma over time.

Association pour la Recherche en Intelligence Artificielle group.

Laboratoire de Biostatistique, Institut Universitaire de Recherche Clinique, Montpellier, France. combesc iurc1.iurc.montp.inserm.fr

Control and severity of asthma are two different but complementary concepts. The severity of asthma could influence the control over time. The aim of this study was to demonstrate this relationship. A total 365 patients with persistent asthma (severity) were enrolled and followed-up prospectively. Data were analysed using a continuous time homogeneous Markov model of the natural history of asthma. Control of asthma was defined according to three health states which were qualified: optimal, suboptimal and unacceptable control (states 1, 2 and 3). Transition forces (denoted lambda(ij) from state i to state j) and transition probabilities between control states were assessed and the results stratified by asthma severity were compared. Models were validated by comparing expected and observed numbers of patients in the different states. Transition probabilities stabilised between 100-250 days and more rapidly in patients with mild-to-moderate asthma. Patients with mild-to-moderate asthma in suboptimal or unacceptable control had a high probability of transition directly to optimal control. Patients with severe asthma had a tendency to remain in unacceptable control. A Markov model is a useful tool to model the control of asthma over time. Severity modified clearly the health states. It could be used to compare the performance of different approaches to asthma management.

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A longitudinal study of adult-onset asthma incidence among HMO members.

Milton DK.

Department of Environmental Health, Harvard School of Public Health, Boston, MA, USA. ssama hsph.harvard.edu

BACKGROUND: HMO databases offer an opportunity for community based epidemiologic studies of asthma incidence, etiology and treatment. The incidence of asthma in HMO populations and the utility of HMO data, including use of computerized algorithms and manual review of medical charts for determining etiologic factors has not been fully explored. METHODS: We identified adult-onset asthma, using computerized record searches in a New England HMO. Monthly, our software applied exclusion and inclusion criteria to identify an "at-risk" population and "potential cases". Electronic and paper medical records from the past year were then reviewed for each potential case. Persons with other respiratory diseases or insignificant treatment for asthma were excluded.Confirmed adult-onset asthma (AOA) cases were defined as those potential cases with either new-onset asthma or reactivated mild intermittent asthma that had been quiescent for at least one year. We validated the methods by reviewing charts of selected subjects rejected by the algorithm. RESULTS: The algorithm was 93 to 99.3% sensitive and 99.6% specific. Sixty-three percent (n = 469) of potential cases were confirmed as AOA. Two thirds of confirmed cases were women with an average age of 34.8 (SD 11.8), and 45% had no evidence of previous asthma diagnosis. The annualized monthly rate of AOA ranged from 4.1 to 11.4 per 1000 at-risk members. Physicians most commonly attribute asthma to infection (59%) and allergy (14%). New-onset cases were more likely attributed to infection, while reactivated cases were more associated with allergies. Medical charts included a discussion of work exposures in relation to asthma in only 32 (7%) cases. Twenty-three of these (72%) indicated there was an association between asthma and workplace exposures for an overall rate of work-related asthma of 4.9%. CONCLUSION: Computerized HMO records can be successfully used to identify AOA. Manual review of these records is important to confirm case status and is useful in evaluation of provider consideration of etiologies. We demonstrated that clinicians attribute most AOA to infection and tend to ignore the contribution of environmental and occupational exposures.

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Interleukin-18 levels in induced sputum are reduced in asthmatic and normal smokers.

Thomson NC.

Division of Immunology, Infection and Inflammation, University of Glasgow, Glasgow, UK.

BACKGROUND: IL-18 is a cytokine which is known to have an important role in the development of a Th1 lymphocyte response. As such, it may have a regulatory role in asthma by modifying Th2 lymphocyte responses. Cigarette smoking may amplify the airway inflammation associated with asthma. OBJECTIVE: This study investigated if IL-18 could be detected in induced sputum from asthmatics and normal subjects and if smoking altered IL-18 levels. METHODS: Induced sputum was obtained from asthmatic (31 smokers, 35 non-smokers) and normal (20 smokers, 20 non-smokers) subjects. All smokers had a smoking history of > or =15 pack years. IL-18 levels in sputum supernatant were measured by ELISA. IL-18 mRNA expression and cellular localization were assessed by quantitative PCR and immunocytochemistry, respectively. RESULTS: Smoking was associated with a significant reduction in IL-18 levels (median (interquartile range) - smokers 20 (0-102) pg/mL vs. non-smokers 358 (50-876) pg/mL, P<0.001). This was more pronounced in asthmatics (smokers, 47 (40-64) pg/mL vs. non-smokers, 530 (30-1484) pg/mL; P<0.001) than in normal subjects (smokers, 25 (0-78) pg/mL vs. non-smokers, 247 (50-656) pg/mL; P<0.01). Within each of the smoking and non-smoking groups there was no significant difference in IL-18 levels between asthmatic and normal subjects. There was no correlation between sputum IL-18 levels and any specific cell type in the sputum samples nor serum IgE levels. IL-18 mRNA expression was reduced in asthmatic smokers compared with non-smokers. IL-18 production was localized to sputum macrophages by immunocytochemistry. CONCLUSIONS: IL-18 is detectable in induced sputum samples from both asthmatic and normal subjects. Cigarette smoking significantly reduces sputum IL-18 levels. This effect is more pronounced in asthmatics than in normal subjects.

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ADAM33 is not associated with asthma in Puerto Rican or Mexican populations.

Gonzalez Burchard E.

University of California at San Francisco, San Francisco, CA 94143-0833, USA.

A recent study identified the ADAM33 gene as a promising candidate contributing to asthma. In Puerto Rican and Mexican populations, we have genotyped six single nucleotide polymorphisms (SNPs) that were used in the Genetics of Asthma in Latino Americans Study. We chose to study these two populations because in the United States, Puerto Ricans have the highest asthma prevalence, morbidity, and mortality and Mexicans the lowest. We used the transmission disequilibrium test to analyze associations between the ADAM33 gene variants and asthma, asthma severity, bronchodilator responsiveness, and total IgE levels using single SNPs, two to six SNP combinations, and specific haplotypes in 583 trios (proband with asthma and both biological parents). We also genotyped matched control samples to allow case-control analyses. None of the transmission disequilibrium test or case-control results showed significant association in either population. We found no evidence for association of single SNPs with asthma severity, bronchodilator response, or IgE levels in Mexicans or in the combined population. Two SNPs showed a modest association in Puerto Ricans, insignificant when the number of comparisons was taken into account. We conclude that the ADAM33 gene is not an important risk factor for asthma or for asthma-associated phenotypes in Mexicans or in Puerto Ricans.

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The expression of stem cell factor and c-kit receptor in human asthmatic airways.

Hamid Q.

Meakins-Christie Laboratories, Royal Victoria Hospital, McGill University, Montreal, Quebec, Canada.

BACKGROUND: Asthmatic airways are characterized by infiltration with a variety of inflammatory cells such as mast cells and eosinophils. Stem cell factor (SCF) is an important activating and chemotactic factor for both mast cells and eosinophils. In addition, it is a critical growth and differentiation factor for mast cells. OBJECTIVES: To investigate the contribution of SCF to the pathogenesis of asthma, we examined the expression of SCF and its receptor c-kit in bronchial biopsies and bronchoalveolar lavage (BAL) specimens obtained from asthmatic subjects (n=13) and non-asthmatic control subjects (n=10). METHODS: SCF and c-kit were detected by in situ hybridization (ISH) and immunocytochemistry (ICC). In order to phenotype the cells expressing SCF and c-kit in asthmatic tissue and BAL cells, combined ISH and ICC were also performed. RESULTS: There was a significant difference (P<0.001) in the SCF mRNA expression in asthmatic airway epithelium (70.38+/-12.33% positive cells) compared with controls (12.7+/-17.21% positive cells). There was also a significant difference in subepithelial SCF-mRNA expression, being higher in asthmatics (P<0.001). A significant difference was also found in c-kit receptor mRNA expression in asthmatic biopsies both in epithelium (P<0.001) and subepithelium (P<0.05) compared with controls. ICC results were consistent with the ISH for both SCF and c-kit receptor from asthmatics and controls. The SCF and c-kit receptor mRNA and immunoreactivity in cells recovered from bronchial washing were also significantly higher in asthmatics compared with controls (P<0.05). While SCF expression was localized predominantly in the epithelial layer in bronchial biopsy tissues, alveolar macrophages were found to be the major source of SCF in bronchial washing from asthmatic subjects. CONCLUSION: The results of this study demonstrate the increased expression of SCF and its receptor, c-kit within human asthmatic airways, which suggests an important role of this cytokine in the pathophysiology of asthma.

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Effect of asthma on sinus computed tomography grade and symptom scores in patients undergoing revision functional endoscopic sinus surgery.

Bradley DT.

Department of Otolaryngology-Head and Neck Surgery, Medical College of Georgia, Augusta 30912, USA.

BACKGROUND: The aim of this study was to determine the influence of asthma on sinus computed tomography (CT) grade, endoscopic appearance, and symptom scores in patients undergoing revision functional endoscopic sinus surgery (FESS). METHODS: Prospective data was collected of patients undergoing revision FESS at a tertiary medical center over a 2-year period. CT scans were graded as per the Lund and Mackay system. Patient symptom scores were recorded from the Sino-Nasal Outcome Test (SNOT 20) inventory and individual symptoms from the Rhinosinusitis Task Force major and minor symptom list were graded on a visual analog scale. RESULTS: Eighty patients underwent revision FESS and 20 of those patients had asthma. The average CT grade in asthmatic patients was 18.6 compared with 11.7 in patients who were nonasthmatic (p = 0.000006). The average SNOT 20 symptom score in patients with asthma was 49.6 and in nonasthmatic patients it was 44.9 (p = 0.238). Both asthmatic and nonasthmatic patients experienced a reduction in SNOT 20 symptom scores at 1 year with reductions of 70% (p = 0.0000) versus 72.6% (p = 0.0000), respectively. CONCLUSION: Patients with asthma undergoing revision FESS had higher sinus CT grades compared with patients without asthma. Asthmatic and nonasthmatic patients had statistically significant reductions in symptoms scores after revision FESS. Asthmatic patients had similar symptomatic relief scores after revision FESS as compared with nonasthmatic patients.

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Epidemiology of respiratory viruses in patients hospitalized with near-fatal asthma, acute exacerbations of asthma, or chronic obstructive pulmonary disease.

Hegele RG.

Department of Medicine, National University of Singapore, Singapore. mdctanwc nus.edu.sg

PURPOSE: We compared the prevalence and spectrum of common respiratory viruses among patients with near-fatal asthma, acute exacerbations of asthma, or chronic obstructive pulmonary disease (COPD), and the relation of these findings to acute respiratory symptoms. METHODS: We obtained adequate samples of respiratory secretions from 17 patients hospitalized with near-fatal asthma, 29 with acute asthma, and 14 with COPD. We used a polymerase chain reaction-based method to test for six common respiratory viruses in samples from endotracheal tube aspirates from patients with near-fatal asthma, and from induced sputum specimens from patients with acute asthma or COPD. Respiratory symptoms (runny nose, sore throat, fever, chills, malaise, and cough) were recorded. Quiescent-phase induced sputum specimens were examined from patients who were initially virus positive. RESULTS: Viral nucleic acids were detected in 52% (31/60) of acute-phase specimens and 7% (2/29) of quiescent-phase specimens examined (P <0.001), with similar proportions of virus-positive patients during the acute phase in the three groups: 59% (10/17) of those with near-fatal asthma, 41% (12/29) with acute asthma, and 64% (9/14) with COPD. Picornavirus (47% [n = 8]) and adenovirus (24% [n = 4]) were most commonly identified in near-fatal asthma, whereas influenza virus (36% [n = 5]) predominated in COPD. Virus-positive patients had a significantly increased frequency of runny nose, sore throat, fever, chills, and malaise (odds ratio = 4.1 to 18; P = 0.02 to 0.001). CONCLUSION: Respiratory viruses are associated with hospitalizations for near-fatal asthma, acute asthma, and COPD, with some differences in the spectrum of viruses involved in the different groups of patients. Respiratory viruses are a target for the prevention and perhaps the treatment of these conditions.

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