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Biomedical subjects

S J Szefler

Publications and source records attributed to S J Szefler.

At least 19 recordsLinked to original sources
PubMed2001

Clarithromycin potentiates glucocorticoid responsiveness in patients with asthma: results of a pilot study.

BACKGROUND: Selected macrolide antibiotics have steroid-sparing effects in patients with steroid-dependent asthma. In addition to inhibiting methylprednisolone clearance, macrolides may also display anti-inflammatory effects. OBJECTIVE: To determine whether clarithromycin, by virtue of its anti-inflammatory effects, enhances glucocorticoid sensitivity. DESIGN: Open-label, pilot study in a paired design (pre- and posttreatment). PARTICIPANTS: Seven patients, mean age 27 (range 15 to 42 years), with mild to moderate asthma under good control. METHODS: Clarithromycin (500 mg) was administered twice daily for 10 days with blood drawn for lymphocyte stimulation assays at baseline, and again upon completion of therapy. Lymphocytes were stimulated with phytohemagglutinin in the presence and absence of increasing concentrations of clarithromycin and dexamethasone (DEX). RESULTS: At baseline, clarithromycin alone did not cause a significant degree of suppression of T-lymphocyte activation, yet clarithromycin significantly enhanced the sensitivity of lymphocytes to suppression by DEX as measured by a shift in the DEX dose-response curve by at least 6-fold (P = 0.04). In addition, a 10-day course of clarithromycin resulted in: 1) a significant decrease in the inhibitory concentration which results in a 50% reduction in proliferation for DEX alone, thereby increasing glucocorticoid sensitivity (P = 0.04); 2) heightened inhibitory effect of clarithromycin alone (P = 0.03); and 3) a sustained suppressive effect with the combination of clarithromycin and DEX on the inhibition of lymphocyte stimulation (P = 0.01). CONCLUSIONS: Clarithromycin acts synergistically with DEX in suppressing lymphocyte activation. In addition, a 10-day course resulted in a significant treatment effect as evidenced by lower inhibitory concentration which results in a 50% reduction in proliferation value for DEX, a heightened response to clarithromycin alone, and a consistent degree of suppression of lymphocyte stimulation when clarithromycin and DEX were used together.

Adolescent↗
PubMed2001

Challenges in assessing outcomes for pediatric asthma.

Although progress has been made in understanding asthma, much remains unknown; as a result, diagnosis and treatment are not optimal. Information is still needed about the natural history of asthma to better understand which patients are at risk of inflammation and at what point during their disease that inflammation occurs. In the case of children, a greater understanding of the disease's natural history is needed to establish criteria for early diagnosis and to evaluate progressive aspects of the disease so that appropriate measures of progression can be defined. The safety of various medications used as long-term controllers must also be evaluated. The growing information about medication effects on asthma provides unique opportunities to design studies that will guide improvement in asthma care. A number of disease outcomes can be used as surrogate markers of clinically significant endpoints, and a number of adverse effects may serve as surrogate markers. The consequences of poor control of pediatric asthma can be observed in a variety of clinical markers, including clinical features of the disease that worsen as it progresses, pulmonary function deterioration, lung hyperexpansion, and inflammation increases. The Childhood Asthma Management Program is an ongoing clinical trial designed to improve the diagnosis and treatment of asthma in children. Its hypothesis is that anti-inflammatory treatment of childhood asthma will not only relieve morbidity but will also improve lung growth.

Asthma↗
PubMed2001

Pharmacokinetics of intranasal corticosteroids.

Topical administration of corticosteroids can reduce the total dose of corticosteroid required to treat the patient and minimize side effects. This logic has led to the development of intranasal corticosteroids (INCS) for allergic and perennial rhinitis. The second generation of these compounds includes beclomethasone dipropionate, budesonide, flunisolide, fluticasone propionate, mometasone furoate, and triamcinolone acetonide. There is evidence that the INCS are effective in rhinitis; however, there is concern about the potential for these compounds to cause growth suppression. In one study, beclomethasone dipropionate significantly reduced growth in children; however, treatment of children with mometasone furoate nasal spray for 1 year showed no signs of growth suppression. It is evident that the differences among INCS lie in their pharmacokinetics. Structural differences among the various INCS influence their metabolism. The goal of INCS therapy is to have a high ratio of topical to systemic activity. The drug delivery device, absorption of the drug, and drug distribution all contribute to effective topical activity of an INCS. In addition, individual drug metabolism and elimination (half-life and drug clearance) also contribute to the therapeutic index of a drug. Overall, the second-generation INCS cause minimal systemic effects at recommended doses.

Absorption↗
PubMed2001

Safety and reproducibility of sputum induction in asthmatic subjects in a multicenter study.

The safety of sputum induction and the reproducibility of measurements in induced sputum in multicenter studies is unknown. We examined the safety of sputum induction in a two-visit, six-center study in 79 subjects with moderate to severe asthma (mean +/- SD FEV(1) 71 +/- 12% predicted, 67% taking inhaled corticosteroids). In addition, we compared the reproducibility of markers of inflammation in induced sputum with the reproducibility of the FEV(1) and the methacholine PC(20). The FEV(1) decreased > or = 20% from the postbronchodilator baseline in 14% of all subjects and in 25% of subjects whose initial prebronchodilator baseline was 40 to 60% of predicted. All subjects responded promptly to additional albuterol treatment, and no subject developed refractory bronchoconstriction requiring treatment other than reversal of bronchospasm in the study laboratory. The reproducibility of measurements of the eosinophil percentage, eosinophil cationic protein, tryptase, and methacholine PC(20) were similar (concordance correlation coefficients of 0.74, 0.81, 0.79, and 0.74, respectively), without any significant among-center effect. We conclude that sputum induction can be performed safely in subjects with moderate to severe asthma in multicenter clinical trials when carried out under carefully monitored conditions. Importantly, we demonstrate that measurement of markers of inflammation in induced sputum is as reproducible as methacholine PC(20) and should prove useful in the assessment of airway inflammation in multicenter clinical trials.

Aged↗
PubMed2001

The utility of peak flow, symptom scores, and beta-agonist use as outcome measures in asthma clinical research.

STUDY OBJECTIVES: Several methods of utilizing peak expiratory flow (PEF) and other markers of disease activity have been suggested as useful in the management of asthma. It remains unclear, however, as to which surrogate markers of disease status are discriminative indicators of treatment failure, suitable for use in clinical trials. DESIGN: We analyzed the operating characteristics of 66 surrogate markers of treatment failure using a receiver operating characteristic (ROC) curve analysis. PARTICIPANTS: Information regarding FEV(1), symptoms, beta(2)-agonist use, and PEF was available from 313 subjects previously enrolled in two Asthma Clinical Research Network trials, in which 71 treatment failures occurred (defined by a 20% fall in FEV(1) from baseline). INTERVENTIONS: None. MEASUREMENTS AND RESULTS: None of the measures had an acceptable ability to discriminate subjects with a > or % fall in FEV(1) from those without, regardless of the duration of the period of analysis or the criteria for test positivity employed. Areas under the ROC curves generated ranged from 0.51 to 0.79, but none were statistically superior. Sensitivity and specificity combinations were generally poor at all cutoff values; true-positive rates could not be raised without unacceptably elevating false-positive rates concurrently. CONCLUSIONS: Studies that seek to detect treatment failure defined by a significant fall in FEV(1) should not use such individual surrogate measures to estimate disease severity.

Adolescent↗
PubMed2001

A review of budesonide inhalation suspension in the treatment of pediatric asthma.

Asthma is recognized as an inflammatory disease, and inhaled corticosteroids are the mainstay of treatment in patients with persistent disease. Until recently, no inhaled corticosteroid was approved in the United States for children aged 4 years and younger, and no practical dosage form was available for infants and young children unable to use metered-dose inhalers effectively. Budesonide inhalation suspension (BIS) is a glucocorticoid with high topical and low systemic activity. In children aged 12 months-8 years, BIS improves asthma symptoms and lung function and decreases the need for breakthrough bronchodilators. Long-term follow-up studies in children concluded that BIS is well tolerated, with little or no effect on growth and hypothalamic-pituitary-adrenal axis function. Thus it is a valuable therapeutic alternative to systemic corticosteroid therapy in infants and young children.

Adrenocorticotropic Hormone↗
PubMed2000

Longitudinal growth in infants and young children treated with budesonide inhalation suspension for persistent asthma.

BACKGROUND: Results of recent growth studies suggest that inhaled glucocorticosteroids may affect growth in children. OBJECTIVE: Three 52-week, open-label extension studies (studies A, B, and C) were conducted to compare the effects of budesonide inhalation suspension (BIS) with conventional asthma therapy (CAT) on long-term safety, including intermediate-term growth, in 3 different pediatric asthma populations. METHODS: Pediatric asthma patients (ages 6 months to 8 years) from 3 multicenter, randomized, 12-week, double-blind, placebo-controlled studies were eligible to enroll in the 52-week, open-label extension studies. The extension studies were multicenter, randomized, open-label, active-controlled, parallel-group studies performed at 26 centers in the United States. Subjects in each extension study were randomized in a 2:1 ratio to receive either BIS or CAT. BIS was initially administered at a dose of 0.5 mg once (studies A and C) or twice daily (study B), with attempts made at each clinical visit to gradually reduce the dose to the minimum effective dose that maintains asthma control, as judged by the investigator. CAT consisted of any available therapy for asthma, including inhaled glucocorticosteroids in studies B and C only. Height SD scores, growth velocity, and skeletal age (only in studies B and C) were examined. RESULTS: In total, 670 subjects were randomized; 223 subjects received CAT and 447 received BIS. Mean ages at entry were 63.0 months and 60.9 months in CAT and BIS groups, respectively. Median total daily doses of BIS ranged from 0.5 to 1. 0 mg and the mean duration of treatment exposure was 304 +/- 119 days and 342 +/- 83 days in CAT and BIS groups, respectively. Changes in height SD scores differed significantly between the BIS and CAT groups in study A (-0.19, P =.003), and there was a small, statistically significant decrease in growth velocity (-0.8 cm/y, P =.002) in the BIS-treated group compared with the CAT group. No significant differences were observed between BIS and CAT groups in the changes in height SD scores or in growth velocities in studies B (+0.10 and +0.7 cm/y, respectively) and C (+0.12 and +0.8 cm/y, respectively). No differences in skeletal age were observed between BIS and CAT groups in studies B and C. CONCLUSION: There was a small, statistically significant decrease in growth velocity in the BIS-treated group compared with the CAT group in the study (study A) where inhaled glucocorticosteroid use was prohibited before entry and in the CAT group during the study. In the studies (B and C) where inhaled glucocorticosteroids were allowed in the CAT group, no differences were observed in height SD scores or growth velocity. The clinical relevance of these effects, including impact on final adult height, remain to be determined in prospectively planned studies that assess growth in children.

Administration, Inhalation↗
PubMed2000

The changing faces of asthma.

Over the last 20 years, the understanding of the pathogenesis of asthma has changed dramatically. Asthma is now seen as a disease of chronic airway inflammation. Consequently, the paradigm of management has expanded from "as-needed bronchodilators" to include maintenance therapy with antiinflammatory medications and action plans. Health care professionals are assessing medications as potential disease-modifying drugs. To do this, they must understand the natural history of asthma and identify the markers of the disease that reflect long-term outcomes. This article reviews the way in which the concept of asthma has changed, the impact of this new knowledge on the basis of medication selection, and the options for evaluating the effect of medications on long-term outcomes. Reevaluating information will continue to expand our horizon of methods to improve asthma management.

Adolescent↗
PubMed2000

Efficacy and safety overview of a new inhaled corticosteroid, QVAR (hydrofluoroalkane-beclomethasone extrafine inhalation aerosol), in asthma.

Chlorofluorocarbon (CFC)-containing inhalers are gradually being phased out and replaced with hydrofluoroalkane (HFA)-based alternatives. The reformulation provided the opportunity to improve the inhalation technology and physical characteristics of corticosteroid formulations. QVAR contains HFA-beclomethasone dipropionate (HFA-BDP) with the steroid in solution rather than suspension, which, in combination with improved inhaler technology, produces an extrafine aerosol with a mass median aerodynamic diameter of 1.1 microm (smaller than the 3.5-4.0 microm found with CFC-BDP). It was predicted and demonstrated that the smaller particle size of QVAR would be deposited in the lung to a greater extent than that found with CFC-BDP, particularly in the small airway, a major site of inflammation. Increased lung deposition of QVAR permits a reduction in dosage relative to CFC-BDP. Clinical evidence confirms that adult and elderly patients required approximately half the dose of QVAR to achieve the same degree of asthma control as with CFC-BDP. In long-term assessments, patients taking CFC-BDP could be switched to QVAR at half the daily dose without exacerbation of their asthma symptoms. QVAR was associated with a low overall incidence of side effects and, at the maximum recommended dose of 640 microg/d, caused no more adrenal suppression than 672 microg/d CFC-BDP.

Administration, Inhalation↗
PubMed2000

The effect of polymorphisms of the beta(2)-adrenergic receptor on the response to regular use of albuterol in asthma.

Inhaled beta-adrenergic agonists are the most commonly used medications for the treatment of asthma although there is evidence that regular use may produce adverse effects in some patients. Polymorphisms of the beta(2)-adrenergic receptor (beta(2)-AR) can affect regulation of the receptor. Smaller studies examining the effects of such polymorphisms on the response to beta-agonist therapy have produced inconsistent results. We examined whether polymorphisms at codon 16 (beta(2)-AR-16) and codon 27 (beta(2)-AR-27) of the beta(2)-AR might affect the response to regular versus as-needed use of albuterol by genotyping the 190 asthmatics who had participated in a trial examining the effects of regular versus as needed albuterol use. During the 16-wk treatment period there was a small decline in morning peak expiratory flow in patients homozygous for arginine at B(2)-AR-16 (Arg/Arg) who used albuterol regularly. This effect was magnified during a 4-wk run out period, during which all patients returned to using as-needed albuterol, so that by the end of the study Arg Arg patients who had regularly used albuterol had a morning peak expiratory flow 30. 5 +/- 12.1 L/min lower (p = 0.012) than Arg/Arg patients who had used albuterol on an as needed basis. There was no decline in peak flow with regular use of albuterol in patients who were homozygous for glycine at beta(2)-AR-16. Evening peak expiratory flow also declined in the Arg/Arg patients who used albuterol regularly but not in those who used albuterol on an as-needed basis. No significant differences in outcomes between regular and as-needed treatment were associated with polymorphisms at position 27 of the beta(2)-AR. No other differences in asthma outcomes that we investigated occurred in relation to these beta(2)-AR polymorphisms. Polymorphisms of the beta(2)-AR may influence airway responses to regular inhaled beta-agonist treatment.

Adolescent↗
PubMed2000

Asthma: the new advances.

There has been significant interest in halting and even reversing the trend of increasing asthma mortality and morbidity. One strategy is to recognize persistent asthma within the first few years of onset and to intervene early with anti-inflammatory therapy. This review summarizes the new information available on asthma pathogenesis that has helped to shape a change in direction of viewing asthma as an episodic disease to one that is chronic in nature. At the root of this change is the recognition that asthma is a chronic inflammatory disease of the airways. Inhaled steroids are recognized as the most potent anti-inflammatory medication available, and they are now profiled as the cornerstone in the management of chronic persistent asthma. This dramatic change in direction has significant implications for the primary care physician, especially the pediatrician, who is most likely to see asthma in its early stages. Recent interest has been directed toward defining a "window of opportunity" for intervention that could significantly affect the course of the disease. Although this may be an exciting opportunity to control the development of asthma, one has to be cognizant of potential risk of early and long-term therapeutic intervention. This review provides a perspective on our present knowledge and the rationale for early intervention, as well as speculates about how this new information will continue to play a role in advancing asthma care and moving toward a "cure" of this disease.

Acetates↗
PubMed1999

Clinical need for a nebulized corticosteroid.

Asthma is a leading cause of morbidity in children, leading to frequent emergency room visits and hospitalizations. In recent years, a steady increase in the number of cases of pediatric asthma has been observed. Mortality rates among children also have increased. The diagnosis of asthma in infants and young children relies on symptoms, and most children become symptomatic before the age of 2 years. The prognosis of an individual child is difficult to predict because of a lack of clear markers; however, respiratory symptoms that begin at, or persist through, the ages of 3 to 4 years are significantly associated with future asthma. The inflammatory nature of asthma has prompted recommendations for the routine use of inhaled corticosteroids for all patients with persistent asthma. Studies have indicated that early initiation of corticosteroid therapy can reduce airway inflammation and may prevent more serious asthma or irreversible obstruction in later years. Although treatment guidelines recommend the use of inhaled corticosteroids in infants and children younger than 5 years of age, metered-dose and dry-powder inhalers may be difficult for this population to use because of a lack of coordination or understanding. In addition, there are no commercially available inhaled corticosteroids for use in children younger than 4 years of age in the United States.

Administration, Inhalation↗
PubMed1999

Pharmacodynamics and pharmacokinetics of budesonide: a new nebulized corticosteroid.

Underutilization of anti-inflammatory agents in the treatment of asthma has received widespread attention. Inhaled glucocorticosteroids are important agents for the management of asthma in children and adults. Budesonide has a high ratio of topical anti-inflammatory to systemic activity and is one of the most extensively used inhaled glucocorticoids. Budesonide inhalation suspension is the first formulation designed to deliver budesonide by way of nebulization for infants and children under 8 years of age with persistent asthma. Budesonide decreases airway hyperresponsiveness and reduces the number of inflammatory cells and mediators present in the airways of patients with asthma. Budesonide appears to be retained within cells, allowing for a once-daily treatment regimen in certain patient groups. After inhalation of nebulized budesonide, absorption is rapid. Data suggest that plasma concentrations of budesonide are similar in adults and children after inhalation of the same nominal dose from a nebulizer. In children 3 to 6 years of age, total systemic availability of budesonide after dosing with a jet nebulizer was approximately 6% of the labeled dose. Budesonide is highly protein bound, undergoes extensive first-pass hepatic metabolism, is metabolized by the liver cytochrome P450 system, and is primarily excreted in the urine as metabolites. In children 3 to 6 years of age, the volume of distribution at steady state of budesonide inhalation suspension is approximately 3 L/kg, with a terminal elimination half-life of 2.3 hours; systemic clearance is approximately 30 mL/kg. The pharmacodynamic and pharmacokinetic properties of budesonide inhalation suspension allow for potent local anti-inflammatory activity with limited systemic exposure.

Administration, Inhalation↗
PubMed1999

Increased T-cell receptor vbeta8+ T cells in bronchoalveolar lavage fluid of subjects with poorly controlled asthma: a potential role for microbial superantigens.

BACKGROUND: T cells are thought to play an important role in the pathogenesis of chronic asthma. The immunologic triggers that contribute to poorly controlled asthma are unknown but may include infectious agents. Superantigens (SAgs), which stimulate T cells expressing selected T-cell receptor (TCR) beta-chain variable (Vbeta) regions, are known to be an important mechanism by which microbes can contribute to T-cell activation and disease pathogenesis. OBJECTIVE: We sought to determine the potential role of SAgs in T-cell activation of patients with poorly controlled asthma. METHODS: We studied the TCR-Vbeta repertoire of bronchoalveolar lavage (BAL) cells and PBMCs from 9 subjects with poorly controlled asthma (FEV1 <75%), 7 subjects with well-controlled asthma (FEV1 >80%), and 8 normal control subjects with the use of anti-TCR-Vbeta-specific mAbs and flow cytometry. RESULTS: Subjects with poorly controlled asthma had a significantly higher expression of Vbeta8(+) T cells in BAL fluid than subjects with well-controlled asthma and normal control subjects (P <.01) and autologous PBMCs (P <.05). Increased Vbeta8(+) BAL T cells were present in CD4(+) (P <.01) and CD8(+) (P <.05) subsets, suggesting activation by SAgs. CONCLUSION: These results indicate that SAgs are a potential trigger of T-cell activation in poorly controlled asthma.

Adult↗
PubMed1999

Reliability of the model MC-311 MDI chronolog.

BACKGROUND: The Model MC-311 MDI Chronolog (Medtrac Technologies, Lakewood, Colo) is an electronic device for monitoring adherence to metered-dose inhalers (MDIs). It is a thermistor-actuated, microprocessor-equipped device that dispenses inhaled medication while recording the date and time of each canister activation. OBJECTIVE: We evaluated the reliability of the MC-311 MDI Chronolog to determine whether the model could accurately record and report the date, time, and number of MDI actuations. METHODS: Twenty-four of the MC-311 Chronologs were discharged at 8 hourly intervals across 8 days. Battery voltage was assessed before and after the experiment. The mouthpieces of 12 Chronologs were washed daily. RESULTS: By using generous criteria for acceptable reliability, only 10 of 24 (42%) were rated as acceptable. None of these 10 Chronologs recorded 320 or greater actuations (mean +/- SD, 293.9 +/- 13.3; range, 266 to 308); all reliable Chronologs underestimated MDI activation. An additional 6 devices had an initial signature of erroneous recordings dating from device initialization. After removing this signature, the remaining data showed acceptable reliability. All the remaining Chronologs judged to be unacceptable showed time series patterns of seizures (ie, bursts of clustered, erroneous records). Seizures were distributed across trial days, were associated with washing, and preceded all 4 cases of battery failure. Damage to the thermistor is the likely cause of seizure-pattern failures. CONCLUSIONS: In summary, because of a combination of a clear underreporting bias with frequent initialization and seizure-pattern failures, the Model MC-311 MDI Chronolog is not recommended for use in clinical care or research

Equipment Failure↗
PubMed1999

Inhibition of methylprednisolone elimination in the presence of clarithromycin therapy.

BACKGROUND: Macrolide antibiotics have long been used as steroid-sparing agents in patients with severe steroid-dependent asthma. Their efficacy and their propensity to potentiate glucocorticoid adverse effects have been attributed in part to their ability to delay glucocorticoid clearance. OBJECTIVE: We sought to determine whether clarithromycin, a newer macrolide antibiotic, can alter the pharmacokinetic profile of oral glucocorticoids and thereby increase the risk of steroid-induced adverse effects. METHODS: An open-label study in a paired design (before and after treatment) was conducted in a hospital-based outpatient clinic. Participants were 6 adult patients (mean age, 30 years) with mild-to-moderate asthma. Prednisone (40 mg/1.73 m2) and methylprednisolone (40 mg/1.73 m2) were given as single randomized doses on consecutive study days before and on days 8 and 9 of a clarithromycin (500 mg twice daily) course. Twelve-hour pharmacokinetic profiles with measurement of plasma methylprednisolone and prednisolone levels were taken before and after clarithromycin therapy. RESULTS: Clarithromycin therapy resulted in a 65% reduction of methylprednisolone clearance and significantly higher mean plasma methylprednisolone concentrations compared with preclarithromycin concentrations but had no significant effect on prednisolone clearance or mean prednisolone plasma concentrations. CONCLUSIONS: Clinicians must be aware of potential drug interactions that could place patients at increased risk for steroid-induced adverse effects. Such an effect has been demonstrated between clarithromycin and methylprednisolone, two drugs that may be administered concomitantly in asthma. To avoid potential steroid-enhancing effects, prednisone should be substituted for methylprednisolone during prolonged courses of clarithromycin therapy.

Adult↗
PubMed1999

The relationships among environmental allergen sensitization, allergen exposure, pulmonary function, and bronchial hyperresponsiveness in the Childhood Asthma Management Program.

BACKGROUND: Sensitivity and exposure to indoor allergens constitutes a risk factor for the development and persistence of asthma in children. OBJECTIVE: Our purpose was to evaluate the relationship between sensitivity and exposure to inhalant allergens and lung function and bronchial responsiveness in a group of children (n = 1041) aged 8.9 +/- 2.1 years with mild to moderate asthma enrolled in the Childhood Asthma Management Program (CAMP). METHODS: With use of the extensive CAMP baseline cross-sectional data on spirometry, bronchial responsiveness, allergen sensitivities, and household allergen levels, the relationship of sensitization and exposure to allergens to lung function and methacholine sensitivity was evaluated. Children who enrolled in CAMP stopped all antiasthma medication except rescue use of albuterol and prednisone for exacerbations during the 5- to 16-week screening period. During the last 2 of these weeks they underwent spirometry and methacholine challenge. Indoor allergen exposures were determined from questionnaires completed by the parent. Household levels of indoor allergens (mite, cat, dog, cockroach, mold) were determined on house dust samples. Allergen sensitivity was determined by percutaneous skin testing with a standard battery of allergens plus locally important pollen and fungal spores. Lung function and bronchial hyperresponsiveness were compared for children sensitive and not sensitive to both indoor and outdoor allergens on skin testing and, if sensitive, for exposed and not exposed to the allergens to which they were positive on skin testing. RESULTS: There was a strong direct correlation between increased sensitivity to inhaled methacholine and skin test sensitivity to tree, weed, Alternaria, cat, dog, and indoor molds. When the relationship was examined by stepwise regression, the skin test sensitivities showing the strongest associations with the concentration of methacholine that caused a 20% fall in FEV(1) were dog (P =.003), Alternaria (P =.01), and cat (P =.05). Children sensitive to any one of the aeroallergens tested were compared for the presence or absence of exposure to that allergen at the time that the methacholine challenge was performed. Those who were sensitive and exposed to weed and cat had greater methacholine sensitivity than those similarly sensitive but not exposed (P =.003 and P =.02, respectively). CONCLUSIONS: Sensitivity to dog or cat dander or Alternaria by skin testing was associated with increased bronchial responsiveness but not decreased lung function in children with mild to moderate asthma. These findings support the important role that sensitization to certain allergens plays in modulating bronchial responsiveness.

Adolescent↗