Methacholine Inhalation Challenge Test Research Articles

Mannitol vs. methacholine in the evaluation of airway responsiveness in bakers' asthma.

Various indirect or direct airway challenge tests are used to measure nonspecific bronchial hyper-responsiveness (NSBHR). The evaluation of NSBHR in diagnosing occupational asthma (OA) is performed, e.g., to monitor the specific inhalation challenge test (SICT). The aim of this study was to preliminarily compare the results of methacholine and mannitol inhalation challenge tests in SICT monitoring in bakers with work-related airway symptoms. Four bakery workers with a suspicion of OA underwent single-blind placebo-controlled SICTs involving workplace allergens, accompanied by the evaluation of NSBHR with mannitol and methacholine, both before and after SICTs. Clinical examinations, spirometry tests, skin prick tests (SPTs) to common aeroallergens and occupational allergens, as well as tests to determine serum specific IgE antibodies to occupational aeroallergens were also performed. Positive SPTs results to occupational aeroallergens were found in all bakery workers, and specific IgE antibodies to flour were detected in 2 subjects. Three patients displayed positive SICT reactions. In all of these 3 patients, airway responsiveness to methacholine increased significantly. In 2 patients, airway reaction to mannitol was significant, whereas in 1 subject there was no increase in NSBHR after mannitol inhalation. The patient with a negative SICT result did not reveal any changes in NSBHR before and after the test, either to methacholine or mannitol. The data obtained by the authors show that there is no clear correlation between the methacholine and mannitol inhalation challenge tests in SICT monitoring. Preliminary results indicate the need for further investigations to evaluate the usefulness of the mannitol challenge test in the diagnostics of OA. Int J Occup Med Environ Health. 2020;33(2):235-9.

Occupational allergic multiorgan disease induced by wheat flour

Bakers are repeatedly exposed to wheat flour (WF) and may develop sensitization and occupational rhinoconjunctivitis and/or asthma to WF allergens.1 Several wheat proteins have been identified as causative allergens of occupational respiratory allergy in bakery workers.1 Testing of IgE reactivity in patients with different clinical profiles of wheat allergy (food allergy, wheat-dependent exercise-induced anaphylaxis, and baker's asthma) to salt-soluble and salt-insoluble protein fractions from WF revealed a high degree of heterogeneity in the recognized allergens. However, mainly salt-soluble proteins (albumins, globulins) seem to be associated with baker's asthma, and prolamins (gliadins, glutenins) with wheat-dependent exercise-induced anaphylaxis, whereas both protein fractions reacted to IgE from food-allergic patients.1 Notwithstanding, gliadins have also been incriminated as causative allergens in baker's asthma.2 We report on a 31-year-old woman who had been exposed to WF practically since birth because her family owned a bakery housed in the same home where they lived. She moved from this house when she was 25 years, but she continued working every day in the family bakery. In the last 8 years she had suffered from work-related nasal and ocular symptoms such as itching, watery eyes, sneezing, nasal stuffiness, and rhinorrhea. These symptoms markedly improved when away from work and worsened at work. In the last 5 years, she had also experienced dysphagia with frequent choking, especially when ingesting meats or cephalopods, which had partially improved with omeprazole therapy. Two years before referral to our clinic, she began to have dry cough and breathlessness, which she also attributed to her work environment. Upper and lower respiratory tract symptoms increased when sifting the WF and making the dough. The patient did not experience gastrointestinal symptoms with ingestion of cereal products. Skin prick test results were positive to grass (mean wheal, 6 mm), cypress (5 mm) and Russian thistle pollen (4 mm), WF (4 mm), and peach lipid transfer protein (6 mm) and were negative to rice flour, corn flour, profilin, mites, molds, and animal dander. Skin prick test with a homemade WF extract (10% wt/vol) was strongly positive (15 mm). Serologic tests yielded the following results: eosinophil cationic protein, 47 ?g/L; total serum IgE, 74 kU/L; specific IgE (ImmunoCAP; ThermoFisher, Uppsala, Sweden) to WF, 7.4 kU/L; barley flour, 1.24 kU/L; and corn, gluten, alpha-amylase, peach, and apple, less than 0.35 kU/L. Specific IgE binding to microarrayed purified WF allergens (WDAI-0.19, WDAI-0.53, WTAI-CM1, WTAI-CM2, WTAI-CM3, WTAI-CM16, WTAI-CM17, Tri a 14, profilin, ?-5-gliadin, Tri a Bd 36 and Tri a TLP, and gliadin and glutamine fractions) was assessed as described elsewhere.3 The patient's serum specifically recognized ?-5-gliadin and the gliadin fraction, and no IgE reactivity was observed to other wheat allergens. Spirometry revealed a forced vital capacity of 3.88 L (88%), an FEV1 of 3.04 L (87%), and FEV1/forced vital capacity of 83%. A methacholine inhalation test was performed following an abbreviated protocol,4 and the results were expressed as PD20 in cumulative dose (mg) of methacholine. Methacholine inhalation challenge test result was positive (0.24 mg cumulative dose) when she was working, and after a 3-month period away from work and with no visits to the bakery house, it gave a negative result. A chest x-ray was normal. Specific inhalation challenge test was carried out in the hospital laboratory by tipping WF from one tray to another for 15 minutes. Spirometry was performed at baseline and at 2, 5, 10, 15, 20, 30, 45, and 60 minutes after the challenge with WF. Peak expiratory flow was measured at baseline and then hourly over 24 hours (respecting sleeping time). A 12% fall in FEV1 was observed at 20 minutes and a 26% drop in peak expiratory flow at 9 hours after exposure to WF,

Comparison of alveolar nitric oxide concentrations using two different methods for assessing small airways obstruction in asthma

Fractional exhaled nitric oxide (F(E) NO) is considered a potentially useful biomarker for airway inflammation. A two-compartment model (2CM) of pulmonary NO dynamics has been used for the evaluation of bronchial NO flux (J'awNO) and alveolar NO concentration (C(A) NO) in asthmatic patients. Recently, the trumpet shape of the airway tree and axial diffusion (TMAD) model has been reported as a modification of the 2CM. This study was designed to determine the validity of C(A) NO measurement using the TMAD model for assessing small airways inflammation in asthma. A total of 52 asthmatic patients and 12 normal control subjects were included in the study. Methacholine inhalation challenge and pulmonary function tests, sputum induction, and exhaled NO measurements at several flow rates were performed. J'awNO and C(A) NO were calculated using both the 2CM (C(A) NO( 2CM) , J'awNO( 2CM) ) and TMAD models (C(A) NO( TMAD) , J'awNO( TMAD) ). Both J'awNO (J'awNO( 2CM) and J'awNO( TMAD) ) and C(A) NO (C(A) NO( 2CM) and C(A) NO( TMAD) ) were significantly higher in asthmatic patients than in control subjects. C(A) NO( 2CM) was significantly correlated with FEV(1) /FVC (r = -0.35, P = 0.01), FEF(25-75) (r = -0.45, P < 0.001) and sputum eosinophils (r = 0.32, P = 0.02). In contrast, C(A) NO( TMAD) was significantly correlated with FEF(25-75) (r = -0.42, P = 0.002) but not with FEV(1) /FVC or sputum eosinophils. C(A) NO( TMAD) is more specific as an indicator of small airways obstruction than C(A) NO( 2CM) . Assessment of small airways obstruction using the TMAD model may clarify the role of the small airways in the pathogenesis of asthma.

Association of serum‐soluble CD26 and CD30 levels with asthma, lung function and bronchial hyper‐responsiveness at school age

There is a need for markers of Th1 and Th2 imbalance in diseases such as asthma. CD30 is an activation marker of Th2 cells, and importance of Th1 marker CD26 was recently found in adult asthma. We studied whether serum-soluble CD30 (sCD30) or serum-soluble CD26 (sCD26) could support early diagnosis of asthma in children at school age. sCD26 and sCD30 were measured in 34 children with clinically confirmed asthma, 31 with possible asthma and in 147 controls. In addition, the associations of flow volume spirometry, methacholine inhalation challenge and free running test results with serum sCD26 or sCD30 were analysed. Serum sCD30 was significantly higher in children with confirmed asthma (mean 91.5 IU/mL, SD 23.0) than in the controls (78.8 IU/mL, 25.9; p = 0.042). No significant differences were found in serum sCD26 levels between the groups. There was a negative correlation of mean mid expiratory flow values with serum sCD26 (r = -0.22, p = 0.0018). Neither methacholine inhalation challenge nor free running test results were associated with serum sCD26 or sCD30. Serum sCD30 was higher in children with asthma. However, marked overlap in serum sCD30 between asthmatic and healthy children limits the usefulness of sCD30 as a diagnostic marker of asthma.

Sensitivity of peak expiratory flow rate for diagnosing bronchial obstruction on methacholine inhalation challenge in school-aged asthmatic children

To study whether forced expiratory volume in 1 s (FEV1) for the diagnosis of bronchial reactivity by means of the methacholine inhalation challenge test could be appropriately replaced by simple measurements of peak expiratory flow rate (PEFR), 75 consecutively referred asthmatic children aged 6–15 y were examined during a symptom-free period. Their baseline FEV1 and PEFR values ranged from 70 to 130% (mean 99.1) and from 77 to 122% (mean 101.4) of those predicted, respectively. The methacholine inhalation challenge was performed with stepwise doubled cumulative doses and both FEV1 and PEFR were measured at each step. Of the 67 children who had a 20% reduction in either test, the fall in FEV1 was achieved after a lower dose of methacholine than the 20% fall in PEFR in 49 cases, after a higher dose in 15 and after the same dose in 3. There was a significant correlation (r= 0:56, p < 0:001) between the changes in FEV1 and PEFR, although considerable scatter was found in the results. The 64 children who had a reduction of 20% in FEV1 showed a corresponding drop in PEFR that varied from 1.8 to 28.8% (mean 15.3), including 9 children for whom this drop was less than 10%. The results indicate that if the challenge test were based on PEFR measurements, the reference values for the test would have to be different.

Validation of a Single Concentration Methacholine Inhalation Provocation Test (SCIPT) in Children

A new method to assess bronchial hyperresponsiveness (BHR) using a single concentration methacholine has already been validated in adults with asthma. Because the geometrical dimensions of the airways in children are different, the results from studies in adults cannot be extrapolated to children. In this study, we validated the single concentration methacholine inhalation provocation test (SCIPT) in children. Twenty-two children performed three methacholine inhalation challenge tests in random order. Two challenges were performed according to the SCIPT: doubling doses (0.03–1.8 mg; maximal cumulated dose 3.6 mg) were administered with an Aerosol Provocation System (Masterscope, Jaeger). The third challenge was performed according to a standard dosimeter method (SDM): doubling doses (0.002–1.8 mg; maximal cumulative dose 3.5 mg) were administered with a DeVillbiss 646 nebulizer. The degree of BHR is expressed as a PD20. A difference of < 1.5 dose step was assumed to be due to intraindividual variation. We found an intraclass correlation of 0.91 between both tests according to the SCIPT and of 0.80 between the SCIPT and SDM. We found, according to the method of Bland and Altman, good agreement when comparing these two challenge tests. The single concentration inhalation provocation test is reproducible and shows good agreement with a standard dosimeter method to test bronchial responsiveness in children.

Use of inhalation corticosteroids (ICS) in children with asthma in general practice

Background:To prevent airway remodelling and the development of irreversible airway obstruction, inhaled corticosteroids (ICS) should be introduced in an early phase of the disease. Dutch guidelines recommend ICS for children with moderate to severe asthma.Aim of the study:To evaluate the use of ICS in relation to the severity of asthma.Methods:We evaluated asthma symptoms during 2 weeks, bronchial hyper-responsiveness (BHR), and the use of ICS in 74 children (age: 7–16) who were previously prescribed anti asthma medication in general practice. BHR was measured by using a Methacholine inhalation challenge test. Doubling doses of methacholine, beginning with 0.03 mg to a maximum of 1.8 mg (cumulated dose max. 3.6 mg), were administered with the Jeager Masterscope, Aerosol Provocation System (APS), medic aid side stream nebulizer. The degree of bronchial responsiveness was expressed as a PD20, a provocation dose that induces a 20% fall in FEV1 from baseline.Results:Thirty-eight children (51%) reported asthma symptoms on four or more days in their 2 weekly diary. Twenty-seven of these children (71%) had moderate to severe BHR (PD20 <300:g). Two of these children did not use ICS at all, fourteen used ICS intermittent, only eleven used ICS as a maintenance therapy.Conclusion:Our data indicate undertreatment of asthma in children. Health care providers, patients and parents should be more aware of the importance of maintenance therapy of ICS. There seems to be considerable room for improvement.

Validation of a single concentration inhalation provocation test (SCIPT) in children

Background:A new method to assess bronchial responsiveness (BR) using a single concentration methacholine has already been validated in adults with asthma1. Since the geometrical dimensions of the airways in children are different, and deposition of the inhaled aerosol also differs in children, results from studies in adults cannot simply be extrapolated to children.Aim of the study:validation of a single-concentration inhalation provocation method in children.Methods:Twenty-three subjects performed three methacholine inhalation challenge tests. The first two challenges according to method A: doubling doses, beginning with 0.03 mg to a maximum of 1.8 mg (maximal cumulated dose 3.6 mg), were administered with the Jeager Masterscope, Aerosol Provocation System (APS), medic aid sidestream nebulizer. The third challenge according method B: doubling doses, beginning with 0.002mg to a maximum of 1.8mg (maximal cumulated dose 3.5 mg), were administered with a Devillbiss 646 nebulizer. The degree of BR is expressed as a PD20. A difference of <1,5 dose step is assumed to be due to intra individual variation.Results:I.C.C. between method A and B is 0.80 and between both tests according method A 0.91. Comparing challenges 1 and 2, and 1 and 3 showed good agreement according to Bland and Altman.2Conclusion:This single concentration method is an accurate method of measuring BR in children.

Determinants of bronchial responsiveness to methacholine at school age in twin pairs.

The methacholine inhalation challenge test (MIC) was used to evaluate bronchial responsiveness in 67 children who were the products of multiple pregnancies when they were 7-15 years old. At birth, 30 (45%) infants had intrauterine growth retardation (IUGR; birth weight <2 SD below normal birth weight, or birth weight difference >1.3 SD between twin-pairs), and 59 (88%) were born before 37 weeks of gestation. None of the children had doctor-diagnosed asthma. The provocative dose of methacholine causing a 20% fall in Wright's peak expiratory flow (WPEF) (PD20) was below 1,000 microg in 10 (15%) children, and they were classified as MIC responders. There were no differences in perinatal or neonatal factors between MIC responders and nonresponders; in particular, MIC responses did not differ between IUGR infants, and children with appropriate growth for gestational age (AGA) at birth. There were seven discordant pairs in which one child was a MIC responder and the other was not; 5 responders were IUGR, and 2 were AGA children (ns). Respiratory tract infections after the neonatal period were equally common in IUGR and AGA children. However, these infections were associated with later bronchial hyperresponsiveness. Doctor-diagnosed respiratory infections, numbers of antibiotic courses, episodes of otitis media, and the need for adenoidectomy, tonsillectomy, and tympanostomy were more common in MIC responders than in nonresponders. We conclude that IUGR was not associated with subsequent bronchial hyperresponsiveness in twin pairs assessed by the MIC test. A significant relationship was seen between bronchial hyperresponsiveness and infections after the neonatal period.

In search of childhood asthma: questionnaire, tests of bronchial hyperresponsiveness, and clinical evaluation

Background: The definition or diagnosis of asthma is a challenge for both clinicians and epidemiologists. Symptom history is usually supplemented with tests of bronchial hyperresponsiveness (BHR) in spite of their...

Effect of apocynin on ozone-induced airway hyperresponsiveness to methacholine in asthmatics

Apocynin is an inhibitor of NADPH oxidase present in inflammatory cells such as eosinophils and neutrophils. We investigated the effect of inhaled apocynin on ozone-induced bronchial hyperresponsiveness in vivo. Seven mild atopic asthmatics participated in a placebo-controlled, cross-over study with two exposures to O 3 at 2-week intervals. Apocynin (3 ml of 0.5 mg/ml) was inhaled 2 times before and 6 times after O 3 exposure at hourly intervals. At 36 h before and 16 h after O 3 exposure, methacholine inhalation challenge tests (Mch) were performed, and PC 20 and maximal % fall from baseline (MFEV 1) were calculated from dose-response curves. O 3-induced change in PC 20 (ΔPC 20) after placebo treatment was −1.94 ± 0.39 DD (mean ± SEM doubling dose Mch) ( p = .001) and apocynin was −0.6 ± 0.33 DD ( p = .17). The difference between apocynin and placebo treatment was 1.3 DD ± 0.42 ( p = .02). O 3-induced ΔMFEV 1 was 11.9 ± 1.5% ( p = .008) during placebo inhalation and 3.85 ± 1.8% during apocynin ( p = .47). Apocynin reduced the ΔMFEV 1 by 8.05% compared to placebo ( p = .025). We conclude that apocynin markedly reduced O 3-induced hyperreactivity for Mch as well as maximal airway narrowing. The results suggest that apocynin may have a role in preventing ozone-induced exacerbations of asthma.

Outcome of children with respiratory symptoms without objective evidence of asthma: a two‐year, prospective, follow‐up study

This study evaluated the outcome of 33 children with asthma‐like symptoms without objective evidence of asthma, and the role of certain factors in predicting the development of clinical asthma in these children. Data on symptom histories, lung functions (flow‐volume spirometry, free running test and methacholine inhalation challenge test) and atopic sensitization (skin prick tests and markers of eosinophilic inflammation) were collected twice with an interval of 2y, and the diagnoses were re‐evaluated after the follow‐up period. Based on the results, it was concluded that one‐third of the children with prolonged or recurrent lower airway symptoms, such as cough or wheeze, either have mild asthma or will develop asthma in the near future. Children who had a significant response [≥10% fall in forced expiratory volume in 1 s (FEV1)] in the free running test formed a risk group for active asthma, whereas other baseline characteristics seemed not to predict the outcome.

Outcome of children with respiratory symptoms without objective evidence of asthma: a two-year, prospective, follow-up study.

This study evaluated the outcome of 33 children with asthma-like symptoms without objective evidence of asthma, and the role of certain factors in predicting the development of clinical asthma in these children. Data on symptom histories, lung functions (flow-volume spirometry, free running test and methacholine inhalation challenge test) and atopic sensitization (skin prick tests and markers of eosinophilic inflammation) were collected twice with an interval of 2 y, and the diagnoses were re-evaluated after the follow-up period. Based on the results, it was concluded that one-third of the children with prolonged or recurrent lower airway symptoms, such as cough or wheeze, either have mild asthma or will develop asthma in the near future. Children who had a significant response [> or = 10% fall in forced expiratory volume in 1 s (FEV1)] in the free running test formed a risk group for active asthma, whereas other baseline characteristics seemed not to predict the outcome.

Effect of ozone exposure on maximal airway narrowing in non-asthmatic and asthmatic subjects.

1. Ozone is a major constituent of air pollution in the summer. Epidemiological studies have demonstrated that there is an increase in hospital admissions for respiratory diseases 1 day after peak levels of ambient ozone. This may be due to an increase in the responsiveness of the airways to bronchoconstrictor stimuli. 2. In the present study we therefore studied the effect of a controlled exposure to ozone on the maximal degree of airway narrowing to a non-specific bronchoconstrictor, methacholine, 12 h after exposure. Both non-asthmatic and mild-asthmatic volunteers were exposed to ozone. 3. The study had a single blind design. Experimental exposures were to filtered air, 0.40 ppm ozone and filtered air respectively, at 1-week intervals. The duration of each exposure was 2 h with alternating periods of 15 min rest and exercise. At 12 h after exposure, methacholine inhalation challenge tests and sputum induction were performed. 4. Twelve hours after exposure to ozone there was a significant increase in the maximal degree of airway narrowing to methacholine (P < 0.02) compared with exposure to air, in non-asthmatic as well as asthmatic subjects. These physiological changes were accompanied by a significant rise in the percentage of neutrophils in induced sputum (P < 0.02). All changes had returned to baseline values 1 week after exposure to ozone. 5. Exposure to ozone causes a transient increase in the maximal degree of airway narrowing to methacholine in both non-asthmatic and asthmatic subjects. These laboratory results, obtained using relatively high ozone exposure in carefully selected subjects, might provide an explanation for the temporal relationship between ambient ozone levels and hospital admissions for asthma.

Bronchial Asthma and Hyperreactivity After Early Childhood Bronchiolitis or Pneumonia

To determine the infantile risk factors and long-term outcome up to 8 to 10 years of age for bronchial asthma and hyperreactivity in children with early-childhood bronchiolitis or pneumonia. Prospective follow-up of three groups of children. University hospital providing primary hospital care and outpatient consultations for all pediatric patients in a defined area. None. The study groups consisted of 62 children with early-childhood bronchiolitis, 29 children with early-childhood pneumonia with no wheezing, and 52 control children. Infantile risk factors were prospectively registered until 2 years of age. Clinical examination, performed 7 to 8 years later, included recording of atopic and asthmatic symptoms from the preceding 12 months. The methacholine inhalation challenge test was used to assess bronchial hyperreactivity, and mean midexpiratory flow results were used to assess bronchial obstruction. Bronchial asthma was present in nine (15%) of the 62 children from the bronchiolitis group, compared with 7% in the pneumonia group and 2% in the control group. Bronchial hyperreactivity indicated by methacholine inhalation challenge was far more common; it was present in 62% of the bronchiolitis group and in 45% of the pneumonia group. Both groups differed significantly from the control group. Decreased mean midexpiratory flow values were observed in 29% and 21% of the bronchiolitis and pneumonia groups, respectively. All 10 asthmatic patients had bronchial hyperreactivity, but only 20% of hyperreactive children had asthma. An analysis of infantile risk factors disclosed only one, an early onset of wheezing, with a significant effect on bronchial hyperreactivity at school age. Elevated IgE values measured during infancy were associated with the development of clinical asthma. The risk of bronchial asthma was increased after infantile bronchiolitis. Moreover, bronchial hyperreactivity was increased after both infantile bronchiolitis and pneumonia. Methacholine inhalation challenge was a sensitive but nonspecific test for diagnosing bronchial asthma. Both bronchiolitis and pneumonia resulting in hospitalization in early childhood distinguish a group of children with an increased risk for long-term lung function abnormalities and pulmonary illnesses.

Relation between bronchial responsiveness to methacholine and levels of IgE antibody against Dermatophagoides farinae and serum IgE in asthmatic children.

The relation between non-specific bronchial responsiveness and allergic sensitivity was evaluated in children with asthma. Bronchial responsiveness was determined by methacholine inhalation challenge test, and was expressed as a provocative concentration of methacholine causing a 20% fall in FEV1 (PC20). RAST titre for Dermatophagoides farinae and serum IgE level were evaluated as parameters of allergic sensitivity. When the PC20 values, RAST titres for D. farinae, and serum IgE levels of 47 asthmatic children and 16 normal controls were compared, the asthmatic children had significantly lower PC20 values and higher D. farinae-RAST titres and serum IgE levels than the normal controls. The correlation analyses in 47 asthmatic children have shown that there is no significant correlation between PC20 values and RAST titres for D. farinae (r = 0.04, P > 0.1) or between PC20 values and serum IgE levels (r = 0.03, P > 0.1). These results suggest that although both bronchial hyperresponsiveness and allergic sensitization may be in some way related to one another in children with asthma, the magnitude of allergic sensitization does not influence the degree of the non-specific bronchial responsiveness.

THE EFFECTS OF AGE ON BRONCHIAL HYPER-RESPONSIVENESS IN CHILDREN USING METHACHOLINE INHALATION CHALLENGE

We studied bronchial responsiveness in 325 asthmatic patients (200 boys and 125 girls, 0 to 18 years old, mean age, 8.7 years) and 133 disease control subjects (67 boys and 66 girls, 0 to 19 years old, mean age, 7.8 years). The bronchial responsiveness was measured by the methacholine inhalation challenge test. Those over six years old took the methacholine challenge using the Astograph method while those aged five or less used, the tcPO2-method. The tcPO2-method, which uses a transcutaneous oxygen pressure monitoring system, is useful for measuring bronchial responsiveness, especially in younger children.Dmin (bronchial sensitivity) was statistically lower in the asthmatic groups than in age-matched disease control groups. St (bronchial reactivity) was not statistically different between the asthmatic and disease control groups. Dmin was statistically lower in children aged 6 to 7 (8.07±1.61unit) than that in children aged 14 to 15 (28.58±5.96unit). The results showed a significant correlation between age and bronchial responsiveness in asthmatic and disease control groups. But there was no significant correlation between age and bronchial reactivity in either group.We found that age has a significant effect on bronchial hyper-responsiveness, especially in young children. When we evaluate the bronchial hyper-responsiveness in young children, we must consider the influence of age.

Terfenadine, a potent histamine H1‐receptor antagonist in the treatment of grass pollen sensitive asthma.

1. We have assessed the effect of a specific histamine H1-receptor antagonist, terfenadine, in the treatment of atopic asthmatics during the grass pollen season. 2. Eighteen mild, grass pollen sensitive asthmatics (10F, 8M, mean +/- s.e. mean age 34.7 +/- 5.6 years), all of whom were controlled on inhaled beta 2-adrenoceptor agonists alone, took part in a 9 week, double-blind, crossover study using terfenadine 180 mg three times daily and placebo. Throughout the study patients recorded peak expiratory flow rate (PEFR) twice daily, symptoms of cough, wheeze, breathlessness and chest tightness (scored 0-3), and their use of bronchodilators. Methacholine inhalation challenge tests were performed each week. Data were analysed by a method suitable for a two group, two period crossover trial with baseline measurements. 3. Terfenadine significantly reduced symptoms of cough by 76.9% (P less than 0.05) and wheeze by 46.9% (P less than 0.02). Symptoms of breathlessness and chest tightness were reduced by 16.8 and 30.3% respectively but these were not statistically significant. Morning and evening PEFR rose by 5.5 (P less than 0.001) and 6.2% (P less than 0.003) respectively on treatment with terfenadine and bronchodilator use fell by 40.3%. A progressive increase in methacholine sensitivity was seen in both treatment groups throughout the study but did not reach statistical significance. 4. We conclude that treatment with terfenadine during the grass pollen season in sensitive asthmatics reduced their symptoms and bronchodilator requirements and produced a modest improvement in their lung function without affecting the development of increased methacholine sensitivity that occurred during the grass pollen season.

Interpretation of the results of methacholine inhalation challenge tests

Methacholine inhalation challenge studies are conventionally expressed as the provocative cumulative dose of methacholine that causes a 20% fall in FEV1 (PD20). This method is widely used and most suitable for expressing results for challenges in subjects with asthma. However, it is impossible to present results in this manner in other circumstances. Normal subjects and many subjects with allergic rhinitis do not have significant bronchial reactivity and will not reach a 20% fall during standard challenge protocols. This limitation precludes the use of this large population in the quantitative analysis necessary in epidemiologic, genetic, or drug studies. To compound this difficulty, a subset of patients with allergic rhinitis may demonstrate a 20% drop but have a subsequent plateau drop in FEV1. Expressing the results of their methacholine challenge with only a PD20 loses valuable information available in the test. We demonstrate that expressing results as the area beneath a dose-response curve provides useful parametric data on all studied subjects and distinguishes among subjects who might otherwise be classified as equivalent when results are expressed solely as a PD20.

In vivo diagnostic testing and immunotherapy for allergy. Report I, Part I, of the allergy panel. Council on Scientific Affairs

The diagnosis and treatment of allergic disease constitute a particularly difficult and complex field in medicine, a field that has been complicated further by the promulgation and the use of unproved procedures and/or the inappropriate use of proved procedures. This report is the first in a series of reports prepared by a multidisciplinary panel appointed by the Council on Scientific Affairs of the American Medical Association. It discusses the necessity for proper clinical trials to generate reproducible results under similar conditions to adequately prove the validity of various diagnostic and therapeutic procedures. In vivo immunologic tests have been shown to be reliable and valid diagnostic tools and include skin tests with standardized allergenic extracts by prick, puncture, and intradermal techniques, skin end-point titration, and patch testing for contact allergic dermatitis. Other clinically useful physiologic tests include the exercise tolerance test, methacholine and/or histamine inhalation challenge test, and other inhalation tests utilizing either nasal or bronchial delivery. Oral challenge testing has also been utilized and includes open, single-blind, or double-blind techniques, depending on the requirements of the patient being studied. The second article is a continuation of the first report, and describes other challenge tests and unproved procedures. The third report of this series evaluates in vitro tests for allergy.