Methacholine Challenge In Children Research Articles

Methacholine challenge in children with sickle cell disease: A case series

Lung disease is a major cause of morbidity in children with sickle cell disease (SCD). Asthma in children with SCD is associated with a twice greater rate of pain and acute chest syndrome (ACS) episodes when compared to children with SCD but without asthma. Provocation challenges with methacholine are used to diagnose asthma when spirometry is normal, bronchodilator reactivity is absent, or the clinical picture is ambiguous. There have been only limited descriptions of use of methacholine challenge in individuals with SCD. We conducted a retrospective cohort study of 21 children with SCD and recurrent respiratory tract symptoms who were challenged with methacholine to determine if airway hyper responsiveness (AHR) was present. Fourteen (67%) of the children had a positive challenge. Of the 14 patients, four were given a new diagnosis of asthma based on the presence of chronic chest symptoms and the newly determined AHR and started on inhaled corticosteroids (ICS). In each positive challenge, forced expiratory volume in one second (FEV(1)) was reversed to at least 90% of baseline 15 min after bronchodilator treatment. Oxygen saturation decreased in 93% of those with a positive challenge, but returned to baseline values 15 min after bronchodilator treatment. No patient developed a pain or ACS episode within at least 1 month after the challenge. Evaluation of AHR with methacholine challenge in patients with SCD appears to be well tolerated and may elucidate a cause of SCD morbidity.

Clinical Utility and Safety of Methacholine Challenge in Children with Sickle Cell Disease.

Introduction: Lung disease is major cause of morbidity in children with sickle cell disease (SCD), yet understanding of lung pathophysiology is lacking. The diagnosis of asthma in children with asthma has become an important consideration in clinical management because of its association with a twice greater the rate of painful and acute chest syndrome (ACS) episodes when compared to children without asthma. Provocation challenges with methacholine have been used in both clinical and research settings to evaluate the presence of degree of airway hyperresponsiveness (AHR) in studies of asthma; however, no such evaluation has been described in children with SCD.Methods: As part of routine clinical care, 21 children with SCD multiple or severe acute chest syndrome (ACS) episodes were challenged with methacholine to determine if AHR was a component of their recurrent respiratory tract symptoms.Results: A total of fourteen of the children had a positive challenge, none of whom had evidence of obstruction or bronchodilator reactivity on spirometry. Ten of fourteen patients were previously on inhaled corticosteroids and had their asthma diagnosis confirmed and four were given a new diagnosis of asthma. In each positive challenge, forced expiratory volume in one second reversed to at least 90% of baseline after bronchodilator treatment. No patient developed a painful or ACS episode temporally related to the challenge.Conclusion: Evaluation of AHR with methacholine challenge in patients with SCD appears to be well tolerated and may elucidate the basis of lung morbidity in a subgroup of children with repetitive or serious ACS episodes.

Airway hyperreactivity detected by methacholine challenge in children with sickle cell disease

Recent studies have emphasized the presence of airway hyperreactivity (AHR) in children with sickle cell disease (SCD). However, various tests for the detection of AHR have yielded distinctly different results in these patients. This study identified AHR via a methacholine challenge test (MCT) in a group of children with SCD (31 patients; age range, 6-16 years). The results of pulmonary function tests (PFTs) in patients with SCD and age-matched controls (30 healthy children) were investigated and compared. A positive methacholine challenge result was noted in 25 patients (77.5%). We found that when compared with controls, the children with SCD had lower forced vital capacity (FVC) and forced expiratory volume in 1 sec (FEV(1)) and that both their forced expiratory flow at 25-75% of the FVC (FEF(25-75)) and their FEV(1)/FVC ratio were not statistically significantly different from those of the controls. The statistically significant differences remained after treatment with a bronchodilator agent, but the changes in the FVC, FEV(1), and FEF(25-75) in response to bronchodilator treatment did not differ with statistical significance between the two groups. There was a negative correlation between the number of ACS attacks and the percent predicted of the FEV(1) and the FEV(1)/FVC ratio. We found that the MCT reveals a high incidence of AHR in patients with SCD, regardless of whether those individuals have ACS.

Airway Hyperresponsiveness to Methacholine at Age 6 to 8 Years in Nonasthmatic Patients Is Not Related to Increased Health-Care Utilization for Asthma in the Ensuing 5 Years: A Longitudinal Study of a Birth Cohort

Children with heightened airway responsiveness have a greater tendency to develop asthma symptoms. Many existing studies describing this relationship have relied on self-reported symptoms that may be prone to recall bias. In addition, few studies have examined the relationship of airway hyperresponsiveness (AHR) to indicators of asthma severity such as health-care utilization. To determine whether a positive response to methacholine challenge in children without current or physician-diagnosed asthma at age 6 to 8 years is predictive of the subsequent onset of asthma requiring medical evaluation or treatment in the ensuing 5 years. Data were obtained from subjects in a population-based birth cohort (n = 835) enrolled from 1987 to 1989, who were members of a large medical group practice component of a health maintenance organization (HMO). We analyzed a subset of subjects (n = 245) who had completed a methacholine challenge at age 6 to 8 years, had no current or physician-diagnosed asthma, and were still served by the same medical group. These children were followed up from the time of methacholine challenge until HMO disenrollment or through June 2001 (ages 11 to 13 years), whichever came first. Pharmacy claims data and diagnostic codes from physician-patient encounters were evaluated for incident asthma. Incident cases of clinical asthma were defined as any child with two outpatient visits or one hospitalization, one emergency department encounter associated with an asthma diagnostic code (ie, 493.XX), or any child filling prescriptions for two bronchodilators or one antiinflammatory asthma medicine. Methacholine responsiveness was interpreted using American Thoracic Society criteria. Asthma incidence did not differ based on methacholine challenge results for children with normal, borderline, and mild AHR. No child in the study demonstrated moderate-to-severe AHR. Our data suggest that AHR with a borderline or weakly positive result in a methacholine challenge in children 6 to 8 years old without current or physician-diagnosed asthma is not related to increased health-care utilization for asthma in the ensuing 5 years.

Effect of Inspiratory Flow on Methacholine Challenge in Children

Regulation of inspiratory flow alters the outcomes of the methacholine (MHC) challenge in adults and cough receptor sensitivity in children. The effect of inspiratory flow on the reproducibility of the MHC challenge in children is unknown. The aim of this study was to evaluate the effect of inspiratory flow alteration on the repeatabilty of the MHC challenge in children with and without asthma. Twenty‐five children undertook the MHC challenge on three different days by using a dosimeter connected to a setup that allowed regulation of inspiratory flow and pattern. Children were randomized to commence the challenges at 20 or 60 L/min, and the last challenge was performed at 20 L/min. The within‐subject standard deviation, 95% range for change, and doubling dose for the differing inspiratory flow (20 vs. 60 L/min) was more than twice that of when inspiratory flow was maintained at 20 L/min for both occasions. The range of the “limits of agreement” of the Bland and Altman plot was smaller when inspiratory flow was constant. For short‐term comparative individual studies in children, inspiratory flow should be regulated. Laboratories and research measuring change in airway hyperrepsonsiveness to MHC should determine and report reproducibility indices of the challenge so airway hyperresponsiveness changes can be interpreted meaningfully.

The role of the methacholine challenge in children with chronic cough

Thirty-nine male and 35 female subjects, aged 6 to 20 years, with chronic cough were studied with spirometry and standard methacholine (MCH) challenge. The duration of their cough before the MCH challenge ranged from 2 months to 13 years. Their FEV 1 ranged 62% to 132% predicted. Thirty-six (49%) patients had a positive MCH challenge. The MCH concentration inhaled to decrease the FEV 1 by 20% ranged from 0.55 to 25 mg/ml. Follow-up data (mean 14 months) were available on all 74 patients. Fifty-four patients received asthma medications, and 93% improved in mean 3.6 weeks. At the end of the follow-up, 22 (30%) were asymptomatic, 39 (53%) were improved, and 13 patients (17%) were symptomatic. We were unable to predict bronchial hyperreactivity in this population on the basis of duration of the cough, personal or family history of allergies, or baseline spirometry. Thus, MCH challenge is helpful in evaluating children with chronic cough and in guiding therapy. Follow-up of children with chronic cough is important. Eleven percent of this study population progressed to develop bronchial asthma. Forty percent of these patients, initially doing well, were asymptomatic at the end of the follow-up period.

Antigen and methacholine challenge in children with asthma

Antigen inhalation challenges for clinical use have 2 essential purposes in my view. One of these, and perhaps the most important, relates to whether the ultimate goal of therapy is directed toward immunotherapy. The second establishes that the lung either is or is not a target organ, regardless of whether the skin test has demonstrated the presence of specific IgE to the antigen. It follows, therefore, that there should and must be clear-cut indications for antigen challenges, which are not without considerable risk in sensitive individuals. Any asthmatic, who clearly has a seasonal history related to his skin tests, probably does not require any antigen challenges. The role of the challenge is essentially twofold-first, the initial confirmation of the lung being sensitive to the antigen and hence responding as bronchospasm; second, following immunotherapy, the response to another challenge would provide pertinent information as to whether the therapeutic procedure (immunotherapy) is having the required benefit over time and hence whether or not the therapy should be continued. In the case of the patient who has clear-cut seasonal symptoms, related to his skin tests and to few of any other nonimmunologic precipitant mechanisms (parasympathetic hypersensitivity, exercise, cold, hyperirritability of the airways to nonimmunologic stimuli, etc.), antigen challenges should be unnecessary. The clinical and physiologic responsiveness during the next appropriate season would be sufficient to demonstrate the effectiveness of immunotherapy or the lack thereof. However, in those asthmatics in whom clear evidence of an immune system involvement is not apparent, despite positive skin tests, because of a noncorrelating history (such as a lack of increasing asthma during high pollen seasons or the presence of perennial asthma, making clear definition of a particular allergen difficult), antigen challenges may be the only