Inhalation Test Research Articles

Maximal Airway Response to Methacholine in Cough-Variant Asthma: Comparison With Classic Asthma and Its Relationship to Peak Expiratory Flow Variability

<h3>Background:</h3> In asthmatic subjects, not only airway sensitivity but maximal airway response are increased on the dose-response curve to methacholine, and peak expiratory flow (PEF) variability is closely related to airway hypersensitivity and maximal airway response. <h3>Objective:</h3> The aims of this study were to compare the prevalence and the level of maximal response plateau between patients with cough-variant asthma (CVA) and those with classic asthma (CA), and to examine the relationship between airway hypersensitivity or maximal airway response and PEF variability in patients with CVA. <h3>Methods:</h3> A high-dose methacholine inhalation test was performed on 83 patients with CVA and on 83 patients with CA matched for provocative concentration of methacholine causing a 20% fall in FEV₁ (PC₂₀). PEF was recorded in the morning and evening for 14 consecutive days in 78 CVA patients, and the amplitude percentage mean was used to express the diurnal PEF variation. <h3>Results:</h3> Fifty-two CVA subjects (62.7%) but only 33 CA subjects (39.8%) showed a maximal response plateau. This difference was significant after correction by the Bonferroni method (corrected p=0.024). Subjects in the CVA and CA groups showing a plateau had significantly different plateau levels (38.0 ± 5.9% vs 42.9 ± 3.9%, corrected p=1.0 × 10^-4). In patients with CVA, no significant relationship was found between PC₂₀ and PEF variability. However, the absence of a maximal response plateau and a higher plateau level were associated with increased PEF variability. <h3>Conclusions:</h3> Maximal airway response may be an important confounder in the relationship between airway hypersensitivity and the clinical expression of asthma. The identification of a maximal response plateau and the level of this plateau in patients with CVA provide information relevant to PEF variability.

Occupational asthma in apprentice adolescent car painters

Occupational asthma (OA) is one of the leading causes of pulmonary diseases and has been extensively studied in adults. Childhood employment, a significant problem in many developing countries, should be studied to determine and evaluate its effects on psychosocial and lung health. In order to investigate the presence of work-related asthma-like symptoms and OA in apprentice adolescent car painters, 72 adolescents between the ages of 15-20 yr studying in Vocational Training Centres of Ankara were investigated using questionnaire, pulmonary function test (PFT), serial peak expiratory flow (PEF) measurements and methacholine inhalation tests. As a control group, 72 adolescents studying in Industrial and Commercial Training Centres located in the same environment were investigated with questionnaire and PFT. Almost 50% of the study group had work-related asthma-like symptoms for which occupational dermatitis history was predictive [odds ratio: 2.9 (1.026-8.13) (95% confidence interval)]. Seventeen of 22 with serial PEF measurements showed a variability of > or =20% and three (4.2%) of 12 tested with methacholine inhalation test had a PC20 < or = 8 mg/ml, which led to the diagnosis of OA. There was no statistically significant difference between study and control groups in terms of PFT. In conclusion, the high prevalence of work-related asthma-like symptoms among adolescent car painters clearly indicates the need for routine follow-up of adolescent workers for lung health.

Inhalation method determines outcome of capsaicin inhalation in patients with chronic cough due to sensory hyperreactivity

Background For patients with idiopathic chronic cough, a subgroup is recognised with respiratory symptoms induced by scents and chemicals. The diagnosis of sensory hyperreactivity (SHR) has been suggested for this group of patients and can be made using a capsaicin inhalation test. The aim of the present study was to compare the results of inhaling capsaicin by tidal breathing with those obtained by the dosimeter method regarding repeatability, agreement, and ability to distinguish patients with SHR from healthy controls. Methods A total of 15 patients with chronic cough due to SHR and 15 healthy control subjects underwent a randomised cross-over protocol and were provoked in a double-blind, randomised fashion with vehicle and two concentrations of inhaled capsaicin, using either the tidal breathing or dosimeter method, in a total of four challenges opportunities, two with each method. Results Patients coughed more and showed more respiratory symptoms than healthy controls with each dose of capsaicin. Compared with tidal breathing, inhalation of capsaicin with the dosimeter method caused a significantly greater number of coughs and respiratory symptoms in both patients and controls. Among the patients, the mean number of coughs after inhalation of 1 mL of capsaicin 0.4 μmol/L from the first provocation with tidal breathing was 12 (95% CI: 7; 17) and after inhalation from the first provocation with the dosimeter method 32 (95% CI: 19; 46) ( P<0.05). Both methods showed good repeatability and similar ability to distinguish patients with SHR from healthy control subjects. Conclusions For patients with SHR, capsaicin cough sensitivity is increased and repeatable. The dosimeter method caused more coughs and other respiratory symptoms than the tidal breathing method, indicating that the methods cannot be used interchangeably. Knowledge of the type of inhalation device used, the particle size, the airflow rate and the inspiratory flow rate are essential when comparing different studies of capsaicin-induced cough.

Direct exposure methods for testing native atmospheres

In vitro studies of adverse cellular effects induced by inhalable substances face a number of problems due to the difficulties in exposing cultured cells of the respiratory tract directly to test atmospheres composed of complex gases and particulate compounds. This paper discusses the characteristics of in vitro work and summarizes the use of different in vitro technologies to determine the adverse effects of inhaled pollutants. The exposure of cells to test atmospheres requires accurate control of the pollutant levels, as well as the close contact of cells and gas without interfering with the medium. Systems which rely on the solution of the gas in the medium overlay do not resemble the exposure conditions in vivo, and may not be suitable for studying, for example, the effects of poorly soluble gases. Exposure to gases or complex mixtures can be performed with roller bottles or flasks on rotating and rocking platforms and, using these techniques, the cells are periodically exposed to the test atmosphere. However, the most promising approach is based on a biphasic cell culture technique, where cells are grown on microporous membranes at an air–liquid interface. Here the cells are nutrified from the basal side of the membrane whilst the apical part with the cultivated cells is in direct contact with the test atmosphere. Based on this culture technique, different exposure systems have been developed and these are described and discussed. Exposure of cells from the respiratory tract to gases or particles is responsible for cell injury or cell activation associated with an overexpression of mRNA and the release of bioactive mediators. Therefore, in vitro studies using such a strategy, in combination with relevant and efficient exposure devices, open up new ways to test native complex gases and aerosols. Furthermore, such an experimental approach is not only suitable for cultivated cells, but it can also be used for exposing bacteria to inhalable test compounds. It is possible to analyze the mutagenic potency of in- and outdoor pollutants and several attempts have been made to determine the induction of revertants in a modified Ames assay after exposure to single gases or complex mixtures.

The Canadian Childhood Asthma Primary Prevention Study: Outcomes at 7 years of age

Avoidance of any one of the individual risk factors associated with childhood asthma has not been successful in preventing its development. The purpose of this study is to determine the effectiveness of a multifaceted intervention program for the primary prevention of asthma in high-risk infants at 7 years of age. Five hundred forty-five high-risk infants with an immediate family history of asthma and allergies were prospectively randomized into intervention or control groups prenatally. Intervention measures introduced before birth and during the first year of life included avoidance of house dust, pets, and environmental tobacco smoke and encouragement of breast-feeding with delayed introduction of solid foods. Assessment of outcomes at 7 years consisted of examination by pediatric allergists, methacholine inhalation tests, and allergy skin tests. At 7 years, 469 of the 545 children were contacted, and 380 returned for further assessment. The prevalence of pediatric allergist-diagnosed asthma was significantly lower in the intervention group than in the control group (14.9% vs 23.0%; adjusted risk ratio, 0.44; 95% CI, 0.25-0.79). The prevalence of allergic rhinitis, atopic dermatitis, atopy (defined as positive skin test reactions to any common allergen), and bronchial hyperresponsiveness (defined as the provocative concentration of methacholine that induced a 20% decrease in FEV 1 from a postsaline value of less than 7.8 mg/mL) were not significantly different between the 2 groups. The prevalence of asthma (defined as wheeze without colds and the presence of bronchial hyperresponsiveness) was also significantly lower in the intervention group compared with the control group (12.9% vs 25.0%; adjusted risk ratio, 0.39; 95% CI, 0.22-0.71). The multifaceted intervention program was effective in reducing the prevalence of asthma in high-risk children at 7 years of age.

Effect of Pet Removal on Pet Allergic Asthma

Allergen avoidance has been recommended in the management of allergic asthma. Very few studies have assessed the effect of pet removal on pet allergic asthma. We examined the effect of pet removal from homes on pulmonary function testing, airway hyperresponsiveness, and medication use. Prospective, nonrandomized, nonblinded observational study. Subjects included 20 symptomatic patients with newly diagnosed pet allergic asthma who were keeping domestic animals, including hamsters, cats, dogs, and ferrets, and were sensitized to the animals. They were treated with inhaled corticosteroids or other medications according to recommendations by level of severity of the Global Initiative for Asthma. Methacholine inhalation tests were performed regularly before and after starting medication. Clinical features were compared between the patients who gave away their pets according to recommendations by the clinician (removal group) and the patients who refused to give away their pets (keeping group). There were 10 patients in both the removal group and the keeping group. After >or= 1 year of follow-up with or without pet removal, a 5.9-fold increase in the provocative concentration of methacholine causing a 20% fall in FEV(1) was observed in the removal group compared with a 2.3-fold increase in the keeping group (p = 0.04). There were no significant differences in the changes in FEV(1) and peak flow variability. Finally, no patient received inhaled corticosteroids in the removal group, whereas all but one of the patients needed beclomethasone dipropionate (mean dose, 600 mug/d) in the keeping group. This study indicates that removal of pets from homes reduces airway responsiveness in patients with pet allergic asthma more than optimal pharmacotherapy alone, thereby enabling a decrease in inhaled corticosteroid doses.

The discovery of cromolyn sodium and its effect on research and practice in allergy and immunology

The discovery of cromolyn sodium and its effect on research and practice in allergy and immunology

Lung function in adults with cystic fibrosis at altitude: impact on air travel

Current guidelines for air travel state that patients with chronic respiratory diseases are required to use oxygen if their in-flight arterial oxygen tensions (Pa,O2) drop below 6.6 kPa. This recommendation may not be strictly applicable to cystic fibrosis patients, who may tolerate lower Pa,O2 for several hours without clinical symptoms. Lung function, symptoms, blood gas levels and signs of pulmonary hypertension were studied in 36 cystic fibrosis patients at altitudes of 530 m and, after 7 h, 2,650 m. A hypoxia inhalation test (inspiratory oxygen fraction 0.15) was performed at low altitude in order to predict high-altitude hypoxaemia. Median Pa,O2 dropped from 9.8 kPa at low altitude to 7.0 kPa at high altitude. Mild exercise at a workload of 30 W further decreased Pa,O2. Two-thirds of all patients exhibited Pa,O2 of <6.6 kPa during exercise and, except for one patient, were asymptomatic. Patients were significantly less obstructed at an altitude of 2,650 m. Low forced expiratory volume in one second at baseline was associated with a low Pa,O2 at altitude. It is concluded that cystic fibrosis patients with baseline arterial oxygen tensions of >8.0 kPa safely tolerate an altitude of 2,650 m for several hours under resting conditions. The risk assessment of low in-flight oxygenation should encompass the whole clinical situation of cystic fibrosis patients, with special attention being paid to the presence of severe airway obstruction.

Deep Inspiration Avoidance and Methacholine Response in Normal Subjects and Patients With Asthma

Deep inspiration (DI) avoidance and time intervals between inhalation and measurement of FEV1 may influence methacholine challenges. (1) To compare the degree of airway response to methacholine when the initial FEV1 measurements are obtained either 30 s or 3 min after inhalation, (2) to evaluate a simplified method to study the influence of DI avoidance before inhalation on the fall in FEV1, and (3) to determine if methacholine has a cumulative effect. Twenty-five patients with asthma and 21 normal subjects without asthma. Four methacholine inhalation tests (MITs) were performed: two standard tidal-breathing MITs, with the first FEV1 measured 30 s (test A) and 3 min (test B) after the end of inhalation; a single-dose MIT, using the last concentration from test B, with no control of DI and the first FEV1 obtained 3 min after inhalation (test C); and an identical single-dose MIT preceded by 20-min of DI avoidance (test D). We compared the provocative concentration of methacholine causing a 20% fall in FEV1 (PC20) from tests A and B (aim 1), the percentage fall in FEV1 from tests C and D (aim 2), and the percentage fall in FEV1 from tests B and C (aim 3). Mean PC20 values from tests A and B were 1.5 mg/mL and 1.0 mg/mL (p = 0.002) in patients with asthma, and 69.8 mg/mL and 29.9 mg/mL (p < 0.0001) in control subjects, respectively. The mean falls in FEV1 for tests C and D were 22.0% and 24.5% (p > 0.05) in patients with asthma, and 22.1% and 38.9% (p = 0.0005) in control subjects, respectively. The mean falls in FEV2 for tests B and C were 30.2% and 22.0% (p = 0.01) in patients with asthma, and 27.5% and 22.1% (p > 0.05) in control subjects, respectively. In both groups, the longer the time interval between the end of inhalation and the first FEV2 measurement, the greater the fall in FEV2 (lower PC20). DI avoidance before inhalation does not enhance the fall in FEV2 in subjects with asthma, while it does in control subjects. Methacholine has a slight cumulative effect that is significant in patients with asthma (p = 0.007).

PAIRED ACUTE INHALATION TEST REVEALS THAT ACETALDEHYDE TOXICITY IS HIGHER IN ALDEHYDE DEHYDROGENASE 2 KNOCKOUT MICE THAN IN WILD-TYPE MICE

Aldehyde dehydrogenase 2 (ALDH2) is an important enzyme that oxidizes acetaldehyde. Approximately 45% of Chinese and Japanese individuals have the inactive ALDH2 genotypes (ALDH2*2/*2 and ALDH2*1/*2); acute inhalation toxicity of acetaldehyde has not been evaluated in these populations. We compared the toxicity between wild-type (Aldh2+/+) and Aldh2-inactive transgenic (Aldh2-/-) mice by using the paired acute inhalation test modified from the acute toxic class method (OECD TG433). Blood acetaldehyde level was measured 4 hr after the inhalation. A pair of Aldh2+/+ and Aldh2-/- mice was put into a chamber and was exposed to 5000 ppm of acetaldehyde. At the start of the inhalation, the mice exhibited hypoactivity and closing of the eyes. Subsequently, symptoms such as crouching, bradypnea, and piloerection were observed. Flushing was observed only in the Aldh2+/+ mice. Symptoms such as tears, straggling gait, prone position, pale skin, abnormal deep respiration, dyspnea, and one case of death were observed only in the Aldh2-/- mice. The symptoms did not change 1 hr after inhalation in the Aldh2+/+ mice. In contrast, in the Aldh2-/- mice, the symptoms became more severe until the end of the inhalation. The blood acetaldehyde level in the Aldh2-/- mice was approximately twice that in the Aldh2+/+ mice 4 hr after inhalation. The Aldh2-/- mice evidently showed more severe toxicity as compared with the Aldh2+/+ mice due to acute inhalation of acetaldehyde at a concentration of 5000 ppm. Acetaldehyde toxicity in Aldh2+/+ and Aldh2-/- mice was estimated and classified one class different. Based on this study, acetaldehyde inhalations were inferred to pose a higher risk to ALDH2-inactive human individuals.

Lung tumorigenicity in A/J and rasH2 transgenic mice following mainstream tobacco smoke inhalation.

Hypothesizing that their respective genetic backgrounds would confer an increased sensitivity to lung tumorigenesis, the plausibility of selected rodent models for the inhalation testing of mainstream tobacco smoke (MTS) was evaluated. Strain A/J and rasH2 transgenic (Tg) mice were exposed to MTS from Kentucky 1R4F research cigarettes using either a whole-body or nose-only exposure regimen. The whole-body regimen consisted of a 20-week exposure period [0.200 mg wet total particulate matter/liter (WTPM/l), 6 h/day, 5 days/week]; nose-only dosing proceeded for 28 weeks [0.040, 0.125, or 0.400 mg WTPM/l, 3 h/day, 5 days/week]. Both regimens included a 16-week recovery period. Gross and microscopic examinations of the lungs were used to evaluate tumor formation, with experimental results supporting the following conclusions: 1. Evaluation of MTS-induced tumorigenicity based on gross evaluation versus microscopic confirmation provides strikingly disparate results, indicating that serial sectioning is necessary for a definitive assessment of lung tumors. 2. While the dosing regimens employed do not allow for a definitive comparison, whole-body exposure appeared to be more effective for inducing statistical changes in tumor multiplicity and incidence compared to nose-only exposure. 3. Exposure-related stress, evidenced as reductions in both body weight gain and background tumor formation, represents a potential confounder during inhalation testing of MTS tumorigenicity, with additional investigation warranted to validate the specificity of exposure-related responses. 4. Comparative findings between A/J and rasH2 Tg mice suggest that the former may be overly sensitive to exposure-related stress, potentially influencing tumorigenic responses.

Comparison between peak expiratory flow rate and forced expiratory volume in one second in the evaluation of children suspected to have asthma.

This study was conducted to evaluate whether forced expiratory volume in 1 second (FEV1) for the diagnosis of bronchial reactivity by means of the free-running exercise test and bronchodilator inhalation, could be appropriately replaced by simple measurements of peak expiratory flow rate (PEFR) in children.We studied 108 referred symptomatic children (due to chronic cough or wheezing) suspected to have asthma aged 5-14y. Forced breathing spirometry and the "Mini-Wright peak flow meter" tests were recorded before and fifteen minutes after the challenge with free- running exercise or bronchodilator (Salbutamol) inhalation, regarding the baseline FEV1 value (FEV1> 80% considered as normal).There was a high correlation between PEFR and FEV1 (in absolute value and percent predicted) measured before and after bronchodilator inhalation test (r = 0.48, P = 0.05) in comparison to the values referred to free- running exercise test (r = 0.26, P = 0.01)."forced breathing spirometry" and "Mini-Wright peak flow" cannot be used interchangeably for diagnosing asthma, and PEFR measurement should remain a procedure for monitoring and following up the patients.

Causative agents of baker's asthma: A clinical and immunologic study

Rationale The causative role of cereal flour, glycolitic enzymes, and egg proteins in bakers with work-related rhinitis and asthma was investigated. Methods Sensitization to baking ingredients was assessed by immunologic tests and confirmed by specific inhalation challenge (SIC). Results Twenty-one bakery workers (20 males; 22 to 60 year-old) with work-related respiratory symptoms were evaluated. They had been working in the baking industry between 2.6 and 46 years. The mean duration of rhinitis and asthma symptoms was 7.66 and 7.05 years, respectively. Sixty-seven percent were atopic and 52% were non-smokers. Methacholine inhalation tests revealed bronchial hyperresponsiveness in all patients but one. Seventeen patients (81%) had positive skin tests (ST) to wheat flour, 76.2% to rye flour, 47.6% to soybean flour, 61.9% to alpha-amylase, 33.3% to hemicellulase, 19% to glucoamylase and 33.3% to storage mites. Twelve patients were exposed to egg aerosols at work. Five of them (41.7%) had positive ST to egg white, 33.3% to ovalbumin, 16.7% to ovomucoid, 41.7% to lysozyme and 25% to egg yolk. SIC tests were performed with wheat flour (n=10), rye flour (n=1), soybean flour (n=6), alpha-amylase (n=12), hemicellulase (n=4), glucoamylase (n=3), ovalbumin (n=2), ovomucoid (n=1) and lysozyme (n=5) in some sensitized workers. Eighty-four percent SIC tests were positive. SIC elicited isolated early asthmatic responses (AR) in 62.1% cases, isolated late AR in 5.4% cases, and dual AR in 32.4% cases. Conclusions Inhalation of cereal flour and baking additives may induce asthmatic reactions in sensitized workers. However, not all bakers sensitized to these agents experienced an asthmatic reaction during SIC.

Three 20‐Minute Interspaced Salbutamol Inhalations as a Test for the Diagnosis of Reversible Airflow Limitation in Adult Asthmatics

Reversible airflow limitation represents an important parameter for the diagnosis of bronchial asthma. The aim of this study was to design a simple and useful test for the detection of reversible airflow limitation. The subjects were 29 patients with asthma and forced expiratory volume in 1 second (FEV1) < 80% predicted. Following baseline spirometry, subjects inhaled 1.5 mg of salbutamol by a nebulizer and then spirometry was performed 20 min later. The procedure was repeated three times. Subsequently, 13 patients received 30 mg of predonisolone orally once daily for 1 week. Spirometry was performed before and after the oral predonisolone therapy, and results were compared with those of salbutamol inhalation test. The mean increase in FEV1 over the baseline was 18.3% after the first salbutamol inhalation, 26.4% after the second inhalation, and 30.2% after the third inhalation. The increases in FEV1 were significant after each inhalation. The mean increases in the maximum expiratory flow rate at 50% (V50) and that at 25% (V25), measured from the flow volume loop, were 53.5% and 46.9% after the first inhalation, but there were no significant changes by repeated inhalations. A significant reversal of airflow limitation was demonstrated in 18 subjects after the first inhalation, 22 subjects after the second inhalation, and 27 subjects after the third inhalation. Improvement in FEV1 after oral predonisolone was equivalent to that after the third inhalation of salbutamol. A test composed of three 20‐min interspaced salbutamol inhalations is useful for the diagnosis of asthma by demonstrating the presence of reversible airflow limitation.

Occupational asthma due to exposure to iroko wood dust

Occupational asthma (OA) from iroko wood has been reported primarily in case reports. To improve understanding of the pathogenesis of OA induced by iroko wood dust. Three groups of woodworkers were included in this study: 9 workers who had clinically proven OA from iroko; 10 asymptomatic woodworkers; and 10 woodworkers with asthma. All patients underwent the following tests: a skin test with an iroko aqueous extract, specific IgE determination, and an iroko bronchial provocation test (IBPT). An eosinophil count was determined before and after the IBPT, and a methacholine inhalation test was performed after avoidance of exposure to iroko. Patients were asked to monitor their peak expiratory flow rates during a week at work followed by a week's vacation. In all patients with a personal history predictive of OA from iroko, a reduction of the peak expiratory flow rate and positivity to the IBPT while working with iroko were present. The latter test result showed a dual response, with a decrease in forced expiratory volume in 1 second from 25% to 32% at 10 minutes and a further decrease from 35% to 43% at 8 hours; at 24 hours, the eosinophil count was higher (P = .046). In 4 patients, the intradermal test results with iroko extract were positive, whereas the skin prick test result and the specific IgE determination were negative in all patients. The methacholine test result was also positive. In the control groups, all the test results with iroko extract were negative. Our data suggest that OA due to iroko wood may be induced by immunologic mechanisms other than IgE-mediated immediate hypersensitivity reactions.

Next Generation Pharmaceutical Impactor (A New Impactor for Pharmaceutical Inhaler Testing). Part I: Design

A new cascade impactor has been designed specifically for pharmaceutical inhaler testing. This impactor, called the Next Generation Pharmaceutical Impactor (NGI), has seven stages and is intended to operate at any inlet flow rate between 30 and 100 L/min. It spans a cut size (D50) range from 0.54-microm to 11.7-microm aerodynamic diameter at 30 L/min and 0.24 microm to 6.12 microm at 100 L/min. The aerodynamics of the impactor follow established scientific principles, giving confident particle size fractionation behavior over the design flow range. The NGI has several features to enhance its utility for inhaler testing. One such feature is that particles are deposited on collection cups that are held in a tray. This tray is removed from the impactor as a single unit, facilitating quick sample turn-around times if multiple trays are used. For accomplishing drug recovery, the user can add up to approximately 40 mL of an appropriate solvent directly to the cups. Another unique feature is a micro-orifice collector (MOC) that captures in a collection cup extremely small particles normally collected on the final filter in other impactors. The particles captured in the MOC cup can be analyzed in the same manner as the particles collected in the other impactor stage cups. The user-friendly features and the aerodynamic design principles together provide an impactor well suited to the needs of the inhaler testing community.

Bronchial Hyperresponsiveness in Adolescents With Long-term Asthma Remission: Importance of a Family History of Bronchial Hyperresponsiveness

The mechanisms responsible for bronchial hyperresponsiveness (BHR) in symptomatic asthma include genetic predisposition and airway inflammation, but the causes of BHR in adolescents with asthma remission are poorly understood. It has been shown that BHR in adolescents with asthma remission was not reduced by prolonged treatment with inhaled corticosteroids, in contrast to the BHR of symptomatic asthma. The aim of this study was to investigate whether family history of BHR may contribute to the persistence of BHR in asthma remission during adolescence. One hundred twenty-six adolescents with long-term asthma remission (neither symptoms nor any medication used during the previous 2 years) and their parents underwent a methacholine inhalation test. The provocative concentration of methacholine causing a 20% fall in FEV(1) (PC(20)) and the bronchial responsiveness (BR) index were calculated for each individual. Sixty-nine adolescents (54.8%) were found to have persisting BHR (PC(20) < 18 mg/mL). The frequency of BHR and the BR index were significantly higher in parents (n = 138) of the BHR-persisting group (28.3% and 1.150 +/- 0.103, respectively [mean +/- 1 SD]) than in parents (n = 114) of BHR-nonpersisting group (16.7% [p = 0.030] and 1.124 +/- 0.088 [p = 0.029], respectively). Furthermore, adolescents (n = 56) with at least one BHR-positive parent were found to have a higher frequency of BHR (66.1% vs 45.7%, p = 0.023) and a higher BR index (1.244 +/- 0.090 vs 1.204 +/- 0.082, p = 0.011) than adolescents (n = 70) with non-BHR parents. Our results suggest that adolescents in asthma remission are more likely to have BHR when there is a family history of BHR. Further studies are needed to examine the possible involvement of genetic factors in the BHR of adolescents in asthma remission.

Clinical features of recurrent and insidious chronic bird fancier's lung

Chronic bird fancier's lung (BFL) can be subgrouped into two types. One subgroup of patients develops interstitial pulmonary fibrosis after recurrent acute episodes (recurrent BFL), and the other subgroup of patients has no history of acute episodes but has slowly progressive chronic respiratory disease (insidious BFL). To define the clinical characteristics of both types of BFL and to provide clues for diagnosis. We performed a retrospective review of the medical records of patients with chronic BFL who were evaluated between October 1992 and March 2001 at the Tokyo Medical and Dental University Hospital in Japan. Patients were evaluated for their clinical characteristics, including history, laboratory, and immunologic findings; imaging; bronchoalveolar lavage; and histologic findings. Thirty-two patients with chronic BFL were included in this study; 15 patients had recurrent BFL and 17 had insidious BFL. The patients with recurrent BFL tended to breed dozens of pigeons in a loft, whereas the patients with insidious BFL were likely to be exposed to smaller birds kept indoors. Specific antibodies against pigeon dropping extracts or budgerigar dropping extracts were positive in 87% of the recurrent BFL cases and 35% of the insidious BFL cases. Antigen-induced lymphocyte proliferation was positive in more than 90% of both groups. The upper lung field was frequently involved in both groups as demonstrated by chest radiographic findings. In all of the patients with insidious BFL, the diagnosis was confirmed by positive laboratory-controlled inhalation test results. Insidious BFL may be misdiagnosed as idiopathic pulmonary fibrosis if a careful history is not taken and antigen-induced lymphocyte proliferation, careful imaging evaluation, and laboratory-controlled inhalation challenge testing are not conducted. In contrast, the clinical findings of recurrent BFL are consistent with hypersensitivity pneumonitis induced by other antigens.

A new agglomerated KSR-592 β-form crystal system for dry powder inhalation formulation to improve inhalation performance in vitro and in vivo

A new agglomerated KSR-592 (steroid) β-form needle-like crystals with lactose system for dry powder inhalation (DPI) was developed to improve inhalation performance with Jethaler ®. The drug agglomerates were prepared by the method of spherical agglomeration in liquid so as to control the particle size and the mechanical strength of agglomerates by changing the agitation speed of the agglomeration system. The agglomerates mixed with lactose particles for the DPI formulation were effectively disintegrated into respirable fine particle in the milling chamber of the device (Jethaler ®) when inhaled. The DPI formulation with these agglomerates exhibited ideal fluidity and provided a larger fine particle fraction (FPF: 29.7%) than the formulation with agglomerates consisting of α-form (plate-like) crystals (24.5%). The air-flow rate of inhalation had no effect on the disintegration properties of these agglomerates, suggesting a reliable inhalation performance in vivo. Further, an in vivo test of the aerosolized KSR-592 (β-form) crystals having the same particle size distribution as those in the aerosol produced by Jethaler ® was conducted by means of a dry powder inhalation testing system using Brown Norway rats. Inhaled KSR-592 (β-form) crystals were found to be uniformly deposited in the lungs of Brown Norway rat sensitized by ovalbumin (OA) and suppressed the increase in eosinophil number in the lungs after OA challenge.

Carmine (E-120)–induced occupational asthma revisited

Background: Occupational asthma (OA) caused by carmine (E-120) has been reported. Objective: We sought to evaluate the prevalence of sensitization and OA at a natural dye processing factory in which 2 workers had been given a diagnosis of carmine-induced OA 6 years previously. Methods: The 24 current employees and one worker who had recently left work because of asthma completed a questionnaire and underwent skin testing (carmine, cochineal, carminic acid, curcuma, annato, and chlorophyll), carmine IgE dot-blot analysis, and methacholine inhalation testing. Workers exhibiting positive occupational skin test responses, work-related asthma, or bronchial hyperresponsiveness underwent specific inhalation challenge and serial peak expiratory flow rate recording. Results: Positive skin test responses to carmine (41.7%), cochineal (29.2%), and carminic acid (4.2%) were observed. Carmine IgE dot-blot results were positive in 4 subjects. No difference in atopy or smoking was observed between occupationally sensitized and nonsensitized subjects. Among the 5 employees reporting work-related asthma, 2 had positive skin test responses, and 4 had bronchial hyperresponsiveness. Five subjects underwent specific inhalation challenges: 2 workers had early asthma responses to carmine and cochineal challenges, and the remaining subjects did not have suggestive peak expiratory flow recordings. The subject who had left his job was given a diagnosis of carmine-induced OA. Conclusion: The prevalence of sensitization and OA caused by carmine was 41.6% and 8.3%, respectively. When the 3 workers who had left their jobs were included, the cumulative incidence of sensitization and OA was 48.1% and 18.5%, resembling the healthy worker effect. Prevention programs to establish the permissible levels of airborne allergen should be implemented. (J Allergy Clin Immunol 2003;111:415-9.)