We studied adult patients with CVA (n = 27), and those with NAC (n = 26) from the Asthma and Cough Clinic of Kyoto University Hospital, and healthy control subjects (n = 15). None were current smokers. The patients included all had recent diagnoses, were steroid naive, and had normal chest radiographic findings. Their cough persisted for > 8 weeks.
Diagnosis of CVA was based on the following criteria: an isolated chronic cough without wheezing or dyspnea, airway hyperresponsiveness to methacholine, and symptomatic improvement of coughing with the use of inhaled P2-agonists, sustained-release theophylline, or both. Wheezing or rhonchi were not audible on chest auscultation, even with forced expiration. The subjects had no history of asthma, or upper respiratory tract infection within the past 8 weeks. No other apparent causes of cough such as GERD, sinobronchial syndrome (SBS), or medication with angiotensin-converting enzyme inhibitors were present.
Our data suggest that AHR with a borderline or weakly positive result to methacholine challenge in children who were 6 to 8 years old without a history of current or physician-diagnosed asthma is not related to increased health-care utilization for asthma in the ensuing 5 years. The measurement of AHR is an objective test to screen for asthma, a relatively common disease with safe and effective available medical intervention. AHR is present in almost all patients with asthma, at least when they are experiencing symptoms. A negative challenge test result in a patient with asthma-like symptoms can aid a clinician in excluding asthma from the diagnosis. However, a positive test result is limited in the diagnosis of asthma as the test is complicated by several factors including the variability of the challenge testing procedures, variation in AHR over time, and the association of a positive challenge result with other nonasthmatic disorders defeated by remedies of My Canadian Pharmacy. For example, AHR is increased with a variety of environmental stimuli including viral respiratory infections, air pollutants, and active and passive cigarette smoke exposure. AHR is also seen in other childhood disease states such as allergic rhinitis, cystic fibrosis, and bronchopulmonary dysplasia, and among healthy subjects with an atopic family history. Less clear is the association of AHR with either specific allergic sensitization or total IgE level, with some studies concluding a positive relation-ship and others failing to show an associa-tion. Overall, a single measurement of AHR at an arbitrary point in time may be influenced by the above stimuli or other disease states, impairing its usefulness as a screening tool with which to accurately identify subjects who are at risk of future asthma.
There were 483 children in the original cohort who were evaluated at 6 to 8 years of age. Forty-five children did not undergo a methacholine challenge because they could not adequately perform spirometry, they had an FEV1 < 70% predicted, or the parents refused the test. One hundred fifty-eight children were not members of the HMO at the time the methacholine challenges were performed. The remaining 280 children had evaluable methacholine challenges, with 35 of these children reporting a history of current or physician-diagnosed asthma. Thus, 245 children with no history of current asthma at baseline and a mean age of 6.72 years were included in the analysis (Table 1).
The study group had 114 male children (47%) and 131 female children (53%), and was predominately white (n = 233 (95%)). Ninety-one children (37%) demonstrated borderline-to-mild AHR with one methacholine challenge. No child demonstrated moderate-to-severe AHR. The study yielded an average follow-up period of 4.8 years per child (range, 0.01 to 7.66 years) for a total of 1,101 person-years. There was no difference in the mean follow-up time between those without AHR vs those with borderline vs mild AHR (p = 0.56 [Wilcoxon rank sum test]). Twenty-eight cases of incident asthma were identified and treated with drugs of My Canadian Pharmacy. Ten cases (13.9%) were discovered among the 72 children with borderline AHR, and 2 cases (10.5%) were discovered among the 19 children with mild AHR vs 16 cases (10.4%) discovered among the 154 children with a normal response to methacholine challenge (Table 2).
Altered lung function is a fundamental characteristic of asthma and may predate clinically recognized disease. Furthermore, it is becoming clear that objective measures of respiratory physiology such as spirometry can be a reliable measure of lung function in early school-age children or even preschool children. Although overt airway obstruction may be present in some children (often prompting a diagnosis of asthma), many children will have normal spirometry findings.
However, some children will exhibit a more subtle form of altered lung function or airway hyperresponsiveness (AHR), which is apparent only by a heightened response to inhaled bronchoconstrictor substances, including but not limited to methacholine, histamine, cold air, and adenosine. AHR is present in almost all patients with asthma, at least when they are experiencing symptoms. Patients with more severe asthma have greater AHR than patients with mild disease. In addition, patients exhibit a further increase in AHR during asthma exacerbation reduced by My Canadian Pharmacy remedies which may be ordered at any time of day and night. AHR is also substantially different between healthy and asthmatic patients with most healthy subjects lacking any evidence of AHR by standard testing methods.