Single-step direct drug provocation testing is safe for delabelling selected non-low-risk penicillin allergy labels.

BACKGROUND: Penicillin allergy labels are prevalent, and removal of incorrect labels improves patient outcomes and health economics. Labels may be classified as "low-risk" or "non-low-risk," of which the symptoms of the latter chiefly suggest immunoglobulin E-mediated etiology. Traditionally, "non-low-risk" allergy labels are evaluated by penicillin skin testing followed by graded multistep penicillin drug provocation testing (DPT). OBJECTIVE: To evaluate the safety of assessing "non-low-risk" labels with single-step direct DPT. METHODS: We consecutively enrolled inpatients and outpatients of a teaching hospital in Sydney, Australia, with penicillin allergy labels requiring penicillin for first-line treatment. Patients were classified as "low-risk" or "non-low-risk" based on the allergy labels. All patients proceeded directly to amoxicillin DPT, unless there was a history of anaphylaxis within 10 years of assessment to a beta-lactam (except for cefazolin) or Gell and Coombs type 2, type 3, or severe type 4 reaction. This was followed by a course of amoxicillin. RESULTS: A total of 149 patients (41 inpatients, 108 outpatients) were enrolled. No patient was excluded from the study. No patient experienced life-threatening reactions to the protocol. There were 85 patients who reported "non-low-risk" allergy labels. One patient developed generalized pruritus and rash that resolved with standard-dose antihistamines, 2 developed delayed benign maculopapular exanthem, and 3 experienced diarrhea during the course of amoxicillin. CONCLUSION: In our cohort, direct single-step DPT was safe, with only 6 patients with "non-low-risk" allergy experiencing benign reactions. We hope that further studies can be performed into single-step direct DPT to evaluate "non-low-risk" penicillin allergy labels. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: LNR/16/HAWKE/452.

Current Asthma Prevalence Using Methacholine Challenge Test in Korean Children from 2010 to 2014.

BACKGROUND: Most epidemiological studies depend on the subjects' response to asthma symptom questionnaires. Questionnaire-based study for childhood asthma prevalence may overestimate the true prevalence. The aim of this study was to investigate the prevalence of "Current asthma" using the International Study of Asthma and Allergies in Childhood (ISAAC) questionnaire and methacholine challenge test in Korean children. METHODS: Our survey on allergic disease included 4,791 children (age 7-12 years) from 2010 to 2014 in Korean elementary schools. Bronchial hyperresponsiveness (BHR) was defined as provocative concentration of methacholine causing a 20% fall in forced expiratory volume in one second (FEV1) (PC20) ≤ 16 mg/mL. "Current asthma symptoms" was defined as positive response to "Wheezing, current," "Treatment, current," or "Exercise, current." "Current asthma" was defined when the subjects with "Current asthma symptoms" showed BHR on the methacholine challenge test or had less than 70% of predicted FEV1 value. RESULTS: The prevalence of "Wheezing, ever," "Wheezing, current," "Diagnosis, ever," "Treatment, current," "Exercise, current," and "Current asthma symptoms" was 19.6%, 6.9%, 10.0%, 3.3%, 3.5%, and 9.6%, respectively, in our cross-sectional study of Korean elementary school students. The prevalence of BHR in elementary school students was 14.5%. The prevalence of BHR in children with "Wheezing, ever," "Wheezing, current," "Diagnosis, ever," "Treatment, current," and "Exercise, current" was 22.3%, 30.5%, 22.4%, 28.8%, and 29.9%, respectively. BHR was 26.1% in those with "Current asthma symptoms." The prevalence of "Current asthma" was 2.7%. CONCLUSIONS: Our large-scale study provides 2.7% prevalence of current asthma in Korean elementary school children. Since approximately one third of the children who have "Current asthma symptoms" present BHR, both subjective and objective methods are required to accurately predict asthma in subjects with asthma symptoms.

In Vivo Allergen-Activated Eosinophils Promote Collagen I and Fibronectin Gene Expression in Airway Smooth Muscle Cells via TGF-ß1 Signaling Pathway in Asthma.

Eosinophils infiltration and releasing TGF-ß1 in the airways has been implicated in the pathogenesis of asthma, especially during acute episodes provoked by an allergen. TGF-ß1 is a major mediator involved in pro-inflammatory responses and fibrotic tissue remodeling in asthma. We aimed to evaluate the effect of in vivo allergen-activated eosinophils on the expression of COL1A1 and FN in ASM cells in asthma. A total of 12 allergic asthma patients and 11 healthy subjects were examined. All study subjects underwent bronchial challenge with D. pteronyssinus allergen. Eosinophils from peripheral blood were isolated before and 24 h after the bronchial allergen challenge using high-density centrifugation and magnetic separation. Individual co-cultures of blood eosinophils and immortalized human ASM cells were prepared. The TGF-ß1 concentration in culture supernatants was analyzed using ELISA. Gene expression was analyzed using qRT-PCR. Eosinophils integrins were suppressed with linear RGDS peptide before co-culture with ASM cells. Results: The expression of TGF-ß1 in asthmatic eosinophils significantly increased over non-activated asthmatic eosinophils after allergen challenge, p < 0.001. The TGF-ß1 concentration in culture supernatants was significantly higher in samples with allergen-activated asthmatic eosinophils compared to baseline, p < 0.05. The effect of allergen-activated asthmatic eosinophils on the expression of TGF-ß1, COL1A1, and FN in ASM cells was more significant compared to non-activated eosinophils, p < 0.05, however, no difference was found on WNT-5A expression. The incubation of allergen-activated asthmatic eosinophils with RGDS peptide was more effective compared to non-activated eosinophils as the gene expression in ASM cells was downregulated equally to the same level as healthy eosinophils.

Pro and Contra: Provocation Tests in Drug Hypersensitivity.

Drug provocation test (DPT) is the controlled administration of a drug to diagnose immune- or non-immune-mediated drug hypersensitivity and the last step for accurate recognition of drug hypersensitivity reactions when the previous diagnostic evaluations are negative or unavailable. A DPT is performed only if other conventional tests fail to yield conclusive results. In each clinical presentation, "to provoke or not to provoke" a patient should be decided after careful assessment of the risk-benefit ratio. Well-defined benefits of DPT include confirmative exclusion of diagnoses of drug hypersensitivity and provision of safe alternatives. However, disadvantages such as safety, difficulty in interpretations of results, lack of objective biomarkers, risks of resensitization, efficiency in daily practice, and lack of standardized protocols, are poorly debated. This review summarizes the current published research concerning DPT, with particular emphasis on the advantages and disadvantages of DPT in an evidence-based manner.

In vivo diagnosis of allergic diseases--allergen provocation tests.

The allergen challenge test has been the mainstay of diagnosis of allergic diseases for a long time since it offers a direct proof of the clinical relevance of a particular allergen for the allergic disease symptoms and severity. Standardisation and availability for daily practice (including safety issues) are still to be refined but most of the challenge tests have safely crossed the border from research tools to diagnostic tests available for daily practice for a well trained clinical staff.

Occupational asthma: an overview.

Occupational asthma is a form of asthma that is often under-diagnosed and under-reported. Unrecognized occupational asthma can lead to progression of disease and increased morbidity. The medical history is a critical element for establishing a diagnosis of OA. The history should include a detailed assessment of the workplace environment, the work process, changes in symptoms in and away from the workplace, and a review of relevant material safety data sheets that may provide clues regarding exposure(s) and the potential cause(s). Objective testing including spirometry pre- and post-bronchodilators, peak expiratory flow rate monitoring in and out of the workplace, provocation testing (i.e., methacholine challenge) to assess for airway hyperresponsiveness, and, if feasible, specific provocation by experienced personnel in a controlled setting to a suspected inciting agent are necessary for confirming a diagnosis. Skin or serologic testing for specific IgE to aeroallergens to assess the worker's atopic status is useful especially when considering certain forms of OA where atopy is a risk factor. Specialized laboratory testing may be useful for specific OA causes. It is important to correctly make the diagnosis of OA as the impact on the worker's future employment and earning power can be significantly affected.

Methacholine challenge testing: improved patient comfort with a 2-tiered protocol.

BACKGROUND: The methacholine challenge test (MCT) is a test of bronchial hyperreactivity used as an aid in the diagnosis of asthma. MCT results are reported as the provocation concentration at which the forced expiratory volume in 1 second (FEV1) decreases 20% (PC20). The requirement for a 20% or greater decrease in FEV1 results in precipitous decreases in FEV1 in some patients. OBJECTIVE: To improve MCT safety without compromising accuracy. METHODS: We performed a retrospective analysis of 879 consecutive MCTs (derivation cohort). A novel protocol for MCT was developed and validated in a cohort of 564 MCTs performed in a second institution. RESULTS: In comparison with a PC20 cutoff of less than 8 mg/mL, a provocation concentration at which the FEV1 decreases 10% (PC10) cutoff of 1 mg/mL or less has a sensitivity of 86%, a specificity of 98%, a positive predictive value (PPV) of 97%, and a negative predictive value (NPV) of 91%. We propose a novel 2-tiered protocol for MCT. If the PC10 is 1 mg/mL or less, bronchial hyperreactivity is present; if the PC10 is greater than 1 mg/mL, the test is continued until the provocative concentration is 8 mg/mL or a 20% decrease in FEV1 is achieved. Compared with the standard protocol, the proposed protocol has a sensitivity, specificity, PPV, NPV, and overall accuracy of 100%, 98%, 97.6%, 100%, and 99%, respectively. The modified protocol would have enabled us to avoid 26 of 42 cases (62%) in which a 40% or greater decrease in FEV1 occurred and would save 0.65 dose for every MCT performed. The 2-tiered protocol performed well in the validation cohort; sensitivity, specificity, PPV, NPV, and overall accuracy were 100%, 98%, 87%, 100%, and 98%, respectively. CONCLUSION: The proposed 2-tiered protocol is accurate, saves time, and avoids precipitous decreases in FEV1.

Bronchial allergen challenge using the Medicaid dosimeter.

BACKGROUND: Bronchial allergen provocations are well established in asthma research. We evaluated the reproducibility of single-concentration, single-step allergen challenges in volunteers with grass pollen allergy. METHODS: Forty-seven subjects underwent bronchial challenges using the aerosol provocation system nebulizer (Medicaid Sidestream) with incremental doses of grass pollen to define the individual allergen dose that causes a 20% drop in FEV(1) (PD(20)FEV(1)). In 39 subjects this procedure was followed by single-step challenges. Early and late asthmatic responses were monitored, and increases in exhaled nitric oxide were measured before and 24 h after single-step challenges. RESULTS: After the first single-step challenge, the maximum drop in FEV(1) was 21.3% ± 8.0. A comparison of the drop in FEV(1) to the initial incremental challenge (29.7% ± 7.5) revealed an intraclass correlation of -0.30 (p < 0.05). In the second single-step challenge, the mean drop in FEV(1) was 20.9% ± 7.2. Compared with the first single-step challenge, the intraclass correlation was 0.37 (p < 0.05) and the 95% limits of agreement according to Bland and Altman were -17.5 to 18.1%. The increases in exhaled nitric oxide revealed substantial agreement in repeated single-step challenges (26.8 ppb ± 27.8 and 21.8 ppb ± 21.9, ICC 0.62, p < 0.001). CONCLUSIONS: The use of aerosol provocation system to calculate the PD(20)FEV(1) allergen is a timesaving procedure and is less prone to errors because only one dilution of the allergen is used. The repeatability in well-defined subjects is excellent to study the mechanisms of allergen-induced airway inflammation and the development of new treatments for allergic diseases.

The use of a direct bronchial challenge test in primary care to diagnose asthma.

Many asthmatics in primary care have mild symptoms and lack airflow obstruction. If variable expiratory airflow limitation cannot be determined by spirometry or peak expiratory flow, despite a history of respiratory symptoms, a positive bronchial challenge test (BCT) can confirm the diagnosis of asthma. However, BCT is traditionally performed in secondary care. In this observational real-life study, we retrospectively analyze 5-year data of a primary care diagnostic center carrying out BCT by histamine provocation. In total, 998 primary care patients aged ≥16 years underwent BCT, without any adverse events reported. To explore diagnostic accuracy, we examine 584 patients with a high pretest probability of asthma. Fifty-seven percent of these patients have a positive BCT result and can be accurately diagnosed with asthma. Our real-life data show BCT is safe and feasible in a suitably equipped primary care diagnostic center. Furthermore, it could potentially reduce diagnostic referrals to secondary care.

Provoked models of asthma: what have we learnt?

Asthma is a chronic inflammatory disease of the airways characterized by physiological abnormalities of variable airflow obstruction and airway hyperresponsiveness (AHR) to a wide variety of physical and inhaled chemical stimuli and the presence of symptoms. AHR is measured by challenging the airways with a variety of agonists and naturally occurring stimuli, which results in constriction of the airway smooth muscle, leading to airway narrowing and airflow limitation. There are two distinct mechanisms by which the airways can narrow to a constrictor stimulus and these are defined by the pathways they take to induce AHR. Direct stimuli are pharmacological agents administered exogenously (such as histamine or methacholine) that act 'directly' on specific receptors on the bronchial smooth muscle to cause constriction. The other mechanism by which the airway can narrow is via the inhalation of indirect stimuli, which include natural stimuli, such as allergen or exercise, and pharmacological agents such as adenosine monophosphate and hyper-osmotic agents (e.g. hypertonic saline or dry powder mannitol). These stimuli induce airway narrowing 'indirectly' by causing the endogenous release of mediators of bronchoconstriction from airway inflammatory cells. Provoked models of asthma have been extremely valuable in understanding the pathobiology of asthma, in aiding diagnosis, in helping to clarify the mechanisms of actions of effective drugs and in the development of new entities to treat asthma. Some provoked models are valuable clinically, particularly those that measure direct AHR, while others, particularly allergen challenge, have been used in animal models and in humans to study the mechanisms of allergen-induced airway inflammation and the associated physiological changes, as well in the development of new drugs for asthma. An emerging role for measurements of AHR is in the evaluation of the optimal treatment for patients with asthma.

Safety of segmental allergen challenge in human allergic asthma.

BACKGROUND: Segmental allergen challenge is widely used to study mechanisms of human allergic asthma. Despite the relatively large dissemination, limited information is available about the safety of this method. OBJECTIVE: Observational, retrospective study to report the adverse events of segmental allergen challenge in a large group of volunteers with asthma. METHODS: In total, 78 cases from several studies performed between 1994 and 2007 were pooled for this analysis. Volunteers underwent allergen challenge using either a fixed dose of allergen (7 cases) or an individually standardized allergen dose defined by an inhaled allergen test before the challenge (71 cases). A subgroup of 13 volunteers underwent repeated challenges, with more than 6 months between the challenges. RESULTS: With a fixed dose instilled during bronchoscopy, 43% of the participants developed wheezing and coughing, requiring 2-6 puffs of a ss(2)-agonist after segmental allergen challenge. In volunteers with individually standardized doses, a ss(2)-agonist was required in only 19% of the cases. No severe adverse events occurred in all cases studied. Volunteers who underwent repeated challenges did not develop more adverse events than those who underwent 1 challenge. CONCLUSIONS: Segmental allergen challenge is a safe tool to study the mechanisms of human allergic asthma, even when repeated challenges are performed in the same patient. It is associated with only a few, tolerable adverse events, especially when the dose of allergen is standardized individually.

Bronchodilator test in extreme old age: Adverse effects of short-acting beta-2 adrenergic agonists with clinical repercussion and bronchodilator response.

OBJECTIVE: To evaluate chronological age as a limiting factor to perform the bronchodilator test, determine significant adverse effects of short-acting beta 2 agonists with clinical repercussions, and assess bronchodilator response in extreme-old-age patients who undergo the spirometry test. METHODS: This is a cross-sectional and retrospective study. The sample was extracted from the database (spirometer and respiratory questionnaire) of a pulmonary function service. Patients over 90 years old were included in the research, and we evaluated their bronchodilator response and its significant adverse effects that may have clinical repercussions related to the bronchodilator. RESULTS: A sample of 25 patients aged 92.12 ± 2.22 years (95% CI, 91.20 - 93.04), with a minimum age of 90 years and a maximum of 97 years and a predominance of females with 72% (18/25). The bronchodilator test was performed in 84% (21/25) of the patients. The bronchodilator response was evaluated in 19 of the 21 patients (90.47%) who underwent the bronchodilator test. Two tests did not meet the criteria of acceptability and reproducibility. No clinical adverse effects were observed with the bronchodilator medication (salbutamol) during or after the exam. CONCLUSIONS: Chronological age is not a limiting factor for the bronchodilator test, short-acting beta-2 agonists did not present adverse effects with significant clinical repercussion and were useful in the diagnosis and therapeutic guidance of extreme-old-age patients.

[Occurrence of delayed symptoms after a challenge test with methacholine]. / Survenue de symptômes tardifs après un test de provocation par la méthacholine.

There are few prospective studies available on the development of delayed symptoms following challenge tests with methacholine (MCT) at the currently recommended doses. The objective of this study was to describe the nature and frequency of respiratory symptoms suggestive of bronchospasm developing within 24hours after a MCT. The study was offered to adult patients who underwent MCT seen consecutively between June and October 2015. Following the test, a questionnaire adapted from the GINA asthma control questionnaire bearing on diurnal and nocturnal symptoms (cough, dyspnoea, wheeze and tightness), was delivered to the patient and the replies collected by telephone 24hours later. Of the 101 patients included (initial FEV1 2.82±0.79L), 46 (46 %) were MCT+ and 55 (54 %) MCT-. Among the MCT-, 4 (7 %) presented with immediate symptoms (S+) and 4 (7 %) with delayed symptoms. Among the MCT+ patients, 36 (78 %) presented with immediate symptoms (P<0.001 compared with the MCT- patients), and 39 (85 %) with delayed symptoms (P<0.001 compared with the MCT- patients). Delayed symptoms developed with a mean of 5h30 after the provocation test. Immediate and delayed symptoms were more frequent in subjects having significant non-specific bronchial hyper-reactivity. Informing patients of the risk of developing delayed symptoms seems useful and allows optimization of their management after a MCT.

Methacholine challenge testing: identifying its diagnostic role, testing, coding, and reimbursement.

Methacholine challenge testing (MCT), also sometimes described as bronchoprovocation testing, is widely performed for both research and diagnostic purposes. MCT is clinically useful when the patient presents with a history of symptoms suggesting asthma, but spirometry findings are normal. Typically, MCT is performed in a pulmonary function laboratory, a clinic, or a physician's office. MCT requires time, effort, and understanding. Two standard testing regimes are identified along with proper coding and reimbursement methodologies.

The safety and efficacy of inhaled dry powder mannitol as a bronchial provocation test for airway hyperresponsiveness: a phase 3 comparison study with hypertonic (4.5%) saline.

BACKGROUND: Inhaled mannitol is a new bronchial provocation test (BPT) developed to improve portability and standardisation of osmotic challenge testing. Osmotic challenge tests have an advantage over the traditional methods of measuring airway hyperresponsiveness using methacholine as they demonstrate higher specificity to identify asthma and thus the need for treatment with inhaled corticosteroids (ICS). The safety and the efficacy of mannitol (M) as a BPT to measure airway hyperresponsiveness were compared to hypertonic (4.5%) saline (HS) in people both with and without signs and symptoms of asthma. METHODS: A phase III, multi-centre, open label, operator-blinded, crossover design, randomised trial, with follow-up. Asthmatics and non-asthmatics (6-83 yr) were recruited and 592 subjects completed the study. Mannitol was delivered using a low resistance dry powder inhaler and HS was delivered using an ultrasonic nebuliser. The FEV1 was measured 60 seconds after each dose of mannitol (5,10,20,40,80,160,160,160 mg) and after each exposure to HS (0.5,1.0,2.0,4.0,8.0 minutes). A 15% fall in FEV1 defined a positive test. Adverse events were monitored and diaries kept for 7 days following the tests. RESULTS: Mean pre-test FEV1 (mean +/- SD) was 95.5 +/- 14% predicted. 296 were positive to mannitol (M+) and 322 positive to HS (HS+). A post study physician conducted clinical assessment identified 82.3% asthmatic (44% classified mild) and 17.7% non-asthmatic. Of those M+, 70.1% were taking ICS and of those mannitol negative (M-), 81.1 % were taking ICS. The % fall in FEV1 for mannitol in asthmatics was 21.0% +/- 5.7 and for the non-asthmatics, 5.5% +/- 4.8. The median PD15 M was 148 mg and PD15 HS 6.2 ml. The sensitivity of M to identify HS+ was 80.7% and the specificity 86.7%. The sensitivity of M compared with the clinical assessment was 59.8% and specificity 95.2% and increased to 88.7% and 95.0% respectively when the M- subjects taking ICS were excluded. Cough was common during testing. There were no serious adverse events. The diarised events were similar for mannitol and HS, the most common being headache (17.2%M, 19%HS), pharyngolaryngeal pain (5.1%M, 3%HS), nausea (4.3%M, 3%HS), and cough (2.2%M, 2.4%HS). CONCLUSION: The efficacy and safety of mannitol was demonstrated in non-asthmatic and clinically diagnosed asthmatic adults and children.

[Induced sputum in children and adolescents with asthma: safety, clinical applicability and inflammatory cells aspects in stable patients and during exacerbation]. / Escarro induzido em crianças e adolescentes com asma: segurança, aplicabilidade clínica e perfil de células inflamatórias em pacientes estáveis e durante exacerbação.

OBJECTIVES: To determine the safety of sputum induction in asthmatic children and adolescents, to characterize sputum inflammatory cells while clinically stable and during exacerbation and to correlate sputum inflammatory cells with peripheral blood eosinophils, serum IgE and the degree of bronchial obstruction. METHODS: Ninety-six asthmatic patients aged 6 to 18 years were recruited for the present cross-sectional study. Spirometry was performed before and after administration of a bronchodilator. Sputum was collected spontaneously or after induction by the inhalation of saline solution at increasing concentrations. Blood samples were obtained for serum IgE and eosinophil quantification. RESULTS: Sputum samples adequate for analysis were obtained from 68 (70.8%) of the patients recruited. No relevant bronchoconstriction was observed during induction. The presence of a larger number of eosinophils in sputum did not correlate with more clinically severe asthma. No correlation was observed between the degree of bronchial obstruction, measured based on FEV1, and inflammatory cells in sputum, peripheral blood eosinophils or serum IgE. Larger numbers of neutrophils were observed in the asthma exacerbation group (p < 0.05). CONCLUSIONS: Sputum induction was found to be a safe procedure for obtaining clinical samples from children and adolescents even during exacerbations, allowing for clinical and functional limitations. The 67% induction success rate was considered satisfactory. In this group of patients, receiving inhaled corticosteroids, eosinophil quantification did not distinguish between the clinical and functional severity of asthma and was independent of the degree of airway obstruction. A proportional predominance of neutrophils was observed in the sputum of patients with asthma exacerbation.

[The development and safety of cough provocation test by capsaicin inhalation].

OBJECTIVE: To assess the application and the safety of capsaicin cough provocation test by dosimeter method. METHODS: Capsaicin inhalation cough challenge test by dosimeter method was performed on 60 healthy volunteers (group A), 11 subjects with upper respiratory infection (group B), 10 patients with gastroesophageal reflux cough (group C) and 10 patients with asthma (group D). Each subject inhaled doubling concentrations of capsaicin (1.95, 3.90, 7.80, 15.6, 31.2, 62.5, 125, 250, 500, 1,000 micromol/L) by a breath-activated dosimeter until the concentration inducing five or more coughs (C(5)) was reached. The lg C(5) was calculated as the cough reflex sensitivity. General lung ventilation and impedance with impulse oscillometry were measured before and after the cough provocation test. RESULTS: There was no serious side effect of the test in all subjects; two subjects complained of slight nausea; one of heartburn, and three of hoarseness. Before the provocation the values of FEV(1) in group A, B, C and D were (3.6 +/- 0.5) L, (3.7 +/- 0.7) L, (2.7 +/- 0.8) L and (2.1 +/- 0.8) L, compared with (3.6 +/- 0.5) L, (3.7 +/- 0.8) L, (2.6 +/- 0.7) L and (2.1 +/- 0.8) L after the test, the differences being not significant (all P > 0.05). Compared with the measurements after provocation, Zrs was (2.6 +/- 0.8) mm Hg.L(-1).s(-1) vs (2.7 +/- 0.8) mm Hg.L(-1).s(-1) in group A, (2.5 +/- 0.5) mm Hg.L(-1).s(-1) vs (2.6 +/- 0.3) mm Hg.L(-1).s(-1) in group B, (2.7 +/- 0.7) mm Hg.L(-1).s(-1) vs (2.7 +/- 0.7) mm Hg.L(-1).s(-1) in group C, (3.3 +/- 1.5) mm Hg.L(-1).s(-1) vs (3.7 +/- 2.0) mm Hg.L(-1).s(-1) in group D, the differences showed no significance (all P > 0.05 respectively). The lg C(5) value was 2.45 +/- 0.46 in group A, 2.51 +/- 0.20 in group B, 1.52 +/- 0.70 in group C, 2.34 +/- 0.56 in group D. Compared with group A, B and D, the lg C(5) value in group C was significantly different (all P < 0.01 respectively). The lg C(5) value showed no significant difference among group A, group B and group D (all P > 0.05). CONCLUSION: Capsaicin inhalation cough provocation test by dosimeter method is a safe and specific tool for measuring cough reflex sensitivity.

Methacholine challenge testing: safety of low starting FEV1. Asthma Clinical Research Network (ACRN).

STUDY OBJECTIVE: The lower limit for the baseline value to initiate methacholine bronchial hyperresponsiveness testing has not been well established. Recommendations have varied from > 1 L to above 80% of predicted. The objective was to determine if an FEV1 < 60% predicted was acceptable. DESIGN: Retrospective analysis of challenges in 88 patients with a baseline FEV1 of < 60% predicted (mean=45.8%; range, 22 to 59%. SETTING: Academic institutions. RESULTS: There were only four individuals whose FEV1 did not return to > 90% of baseline following one poststudy beta2-agonist treatment. All four responded to a second treatment. There were no adverse sequelae following challenge in any individual. Neither age (up to 79 years) nor gender influenced outcome. CONCLUSIONS: In chronic moderate to severe asthma, it appears that bronchial hyperresponsiveness testing can be safely performed even in those patients with a low baseline FEV1.

Bronchodilator reversal of bronchospasm and symptoms incurred during methacholine bronchoprovocation challenge. Documentation of safety and time course.

We undertook a prospective study of bronchoprovocation challenge (BPC) to look at issues of safety and reversibility of bronchospasm and symptoms induced by BPC. Over a 14-month interval, we documented 62 consecutive cases of bronchial hyperresponsiveness. During BPC, there was a statistically significant but clinically modest increase in both cough and dyspnea. Both bronchospasm and symptoms were readily reversed with a simple protocol of inhaled albuterol using a metered-dose inhaler with a spacer. Routine protocol was effective in every case; there was never a need for individualized physician intervention. Our prospective data document the safety of BPC; we could find no reason why BPC would need to be confined to the hospital. We conclude that BPC is a valuable clinical test which merits wider dissemination and use.