Histamine Challenge Research Articles

S4 Occupational asthma; is this the cause of excess respiratory symptoms and COPD described in bitumen exposed workers?

IntroductionEpidemiological studies suggest increased risk of asthma and COPD in asphalt exposed workers.1 Bitumen is used in this industry. In this case we describe occupational asthma caused by bitumen exposure...

Specificity and detection limit of a dermal temperature histamine sensitization test for absence of residual pertussis toxin in vaccines

Currently, an assay based on fatal sensitization of mice to histamine challenge is widely used for testing absence of residual pertussis toxin in acellular pertussis containing vaccines. For replacement of this lethal end-point assay, an alternative method based on body temperature measurement in mice has been presented, and in this study the specificity and detection limit of a dermal temperature-based assay were assessed. Test preparations containing pertussis toxin were prepared in aluminum-adjuvanted pertussis toxoid vaccine and injected intraperitoneally in histamine sensitive mice. Later the mice were challenged with histamine and the pertussis toxin-induced decrease in dermal temperature recorded. By comparison of mice treated with pertussis toxoid vaccine spiked with pertussis toxin with mice treated with pertussis toxoid vaccine alone, the assay gave a response that specifically could detect presence of pertussis toxin. The acellular pertussis containing vaccine did not interfere with the pertussis toxin-induced temperature response recorded. In tests for presence of pertussis toxin in the pertussis vaccine preparation, the detection limit of the assay was estimated to approximately 5 ng pertussis toxin per human dose of pertussis toxoid. The dermal temperature-based assay was found to be a valid method to be applied in routine quality control of vaccines.

The Impact of <i>Helicobacter Pylori</i> Infection on Lung Function and Severity of Bronchial Hyperresponsiveness in Subjects with Allergic Asthma

Problem statement: There is evidence that Helicobacter pylori (H. pylori) infection may modify immune response and decrease the risk of asthma and other allergic diseases, as well. Approach: To assess the impact of H. pylori infection on lung function parameters and severity of Bronchial Hyperresponsiveness (BHR) in subjects with allergic asthma. A cross-sectional study including 38 H. pylori positive subjects with allergic asthma (18 males and 20 females, aged 21-54 years) and an equal number of H. pylori negative subjects with allergic asthma studied as a control was carried out. The impact of H. pylori infection was assessed by comparison of mean values of spirometric parameters and BHR severity (measured by histamine challenge and expressed as provocative concentration of histamine that causes FEV1 fell by more than 20% of its base value-PC 20) between two examined groups. Results: The mean values of spirometric parameters were similar in both examined groups. The mean PC20 was lower in the group of subjects with allergic asthma and serological evidence of exposure to H. pylori but statistical significance was not reached (2.89 Vs. 3.14 mg mL-1, P > 0.05. Conclusion: Our findings indicate that in cross-sectional analysis there is no significant relation between H. pylori seropositivity and the values of spirometric parameters and the degree of BHR severity in subjects with allergic asthma.

Ten-Year Follow-Up of Early Intensive Self-Management Guidance in Newly Diagnosed Patients with Asthma

Objective. We assessed the 10-year effectiveness of self-management guidance in a prospective follow-up study of patients with asthma when inhaled corticosteroids were used from the beginning in the treatment. Methods. Consecutive newly diagnosed asthmatics (n = 162) were randomized: 80 to an intervention group (IG) and 82 to a control group (CG). Lung function (LF), airway hyperresponsiveness (AHR), and health-related quality of life (HRQoL) were examined at 10 years. Results. The advantages of intensive education with regards to LF measured by forced expiratory volume in 1 second and forced vital capacity were seen only after the first year. Later, there were no statistically significant differences in any parameters between the groups. However, during 10-year follow-up, peak expiratory flow, AHR, and HRQoL improved significantly in both groups (no differences as regards gender, smoking, or atopy). At 10 years, 68% of the IG and 75% of the CG patients still showed AHR after histamine challenge. Generic HRQoL scores in both groups equaled that of the age-standardized group a general population but only 50% in the IG and 55% in the CG had normal disease-specific HRQoL scores. According to Global Initiative for Asthma (GINA) criteria 23% of patients in the IG and 25% in the CG had asthma under control. Conclusions. The effectiveness of intensive self-management education could be shown only in the short term. The groups did not differ significantly in any of the parameters investigated, and showed nearly normal LF and HRQoL. AHR improved only partly and only a minority of the patients had asthma under good control according to GINA criteria. This study showed that evaluation of asthma using LF alone does not show the whole truth about asthma treatment results. HRQoL should be used in conjunction with GINA criteria, to assess asthma treatment outcomes. The value and importance of AHR for the evaluation of treatment remains obscure.

The effect of caffeinated coffee on airway response to methacholine and exhaled nitric oxide

The bronchoprotective effect of caffeine on histamine challenge testing (HCT) has been studied with equivocal results. Current guidelines for bronchoprovocation testing recommend exclusion of caffeine the day of testing. The effects of caffeine on methacholine challenge testing (MCT), now more commonly performed than histamine challenge, are unknown. Sixteen well-controlled asthmatics with a forced expiratory volume in 1 s (FEV(1)) > 65% predicted and methacholine provocation concentration causing a 20% fall in FEV(1) (PC(20)) ≤ 16 mg/ml participated in a randomized single-blind crossover study. The two treatments included 16 ounces of caffeinated and decaffeinated coffee given on two separate days. The fraction of exhaled nitric oxide (eNO) and FEV(1) were measured before and 1 h after each treatment. One hour post treatment blood was drawn for serum caffeine level and the MCT was done. Fourteen subjects completed the study; there were no adverse events. No significant bronchodilation was seen between the mean FEV(1) values before and after the caffeinated treatment (3.31 ± 0.75 L and 3.36 ± 0.74 L, respectively). No significant bronchoprotection was seen between the caffeinated and decaffeinated treatment's geometric mean PC(20) values (1.35 mg/ml and 1.36 mg/ml, respectively). Mean eNO values before and after caffeinated treatment were not significantly different (31.2 ± 19.6 ppb and 31.5 ± 20.4 ppb). The amount of caffeine in a normal dietary serving of a 16 oz cup of coffee is not enough to cause significant bronchoprotection, bronchodilation, or decrease eNO values. Registered at http://clinicaltrials.gov: NCT01057875.

Synthesis and antihistaminic activity of 3 H-benzo [4,5] thieno [2,3- d][1,2,3] triazin-4-ones

In the present study the antihistaminic activity of tricyclic benzothieno 1,2,3-triazine derivatives namely CP-3 (3-(phenyl)-5,6,7,8-tetrahydro,3 H-benzo[4,5] thieno [2,3- d][1,2,3] triazin-4-one), CP-5 (3-(3-methyl phenyl)-5,6,7,8-tetrahydro,3 H-benzo[4,5] thieno [2,3- d][1,2,3] triazin-4-one) and CP-8 (3-(4-chloro phenyl)-5,6,7,8-tetrahydro,3 H-benzo[4,5] thieno [2,3- d][1,2,3] triazin-4-one) were evaluated using in vitro (isolated guinea pig ileum) and in vivo (bronchodilator activity in guinea pigs) models and the sedative potential of the test compounds were evaluated using actophotometer in mice. In in vitro antihistaminic study, the CP-3, CP-5, CP-8 and chlorpheniramine maleate (CPM) have shown a rightward shift in concentration response curve (CRC) of histamine with a change in EC 50 values of histamine in all the four tissue preparations. The slope obtained in the schild plot indicated that CP-5, CP-8 and CPM were competitive in nature for H 1-receptors. However, CP-3 has shown non-competitive antagonism. In in vivo antihistaminic study, the CP-3, CP-5, CP-8 and CPM have shown mean increase in exposition time against histamine challenge compared to control group ( p < 0.001). All the test drugs (10 mg/kg) and CPM (2 mg/kg) have offered a significant ( p < 0.001) protection against preconvulsive dyspnoea (PCD) compared to control. In conclusion, all the test drugs have shown very good antihistaminic activity and the test drugs have very little sedative action compared to CPM.

Exercise-induced bronchoconstriction and exercise-induced respiratory symptoms in nurses.

In order to assess prevalence and characteristics of exercise-induced respiratory symptoms (EIRSs) and exercise-induced bronchoconstriction (EIB) in health care workers, we performed a cross-sectional study including 48 female nurses from primary care settings and an equal number of female office workers studied as a control group. The evaluation of examined groups included completion of a questionnaire, skin prick tests to common inhalant allergens, spirometry, and exercise and histamine challenge. We found a similar prevalence of EIRSs and EIB in both groups. EIB was closely related to asthma, atopy, family history of asthma, and positive histamine challenge in either group, while the association between EIB and daily smoking in nurses was of borderline statistical significance. Bronchial reaction to exercise was significantly higher in nurses than in controls with EIB. With the exception of exercise induced wheezing, EIRSs were weakly associated with EIB in both groups with a large proportion of false positive results.

Outcome of Oesophageal Atresia Beyond Childhood

Esophageal atresia; Esophageal dysmotility; Esophagitis; Gastresophageal reflux; Long-term outcome; Metaplasia The overall survival rate of patients with esophageal atresia (OA) has increased significantly during the last decades, and today exceeds 90% of all patients. 1 Today, practically all patients without concomitant severe malformations survive, and the very high mortality of very low birth weight patients and patients with severe cardiac malformation has decreased significantly. Many surviving patients, however, continue having functional problems, especially from their gastrointestinal tract and respiratory system after the initial postoperative period. 2 The overall impact of these problems on the long-term outcome of OA patients is not fully understood. Moreover, it is unclear what impact postnatal postoperative, usually relatively long hospitalization time, and repeated anesthesias for anastomotic dilations in many patients may have on later psychosocial well-being of the patients. There are a limited number of reports concerning longterm outcome of patients with OA. The eventual quality of life appears to be good in most adults. 3,4 This assumption is

Utility of inhaled allergen challenge in clinical diagnosis and management of asthma: What never? Well, hardly ever!

Cite this as: D. S. Robinson, Clinical &amp; Experimental Allergy, 2011 (41) 606–608.

Utility of nitric oxide for the diagnosis of asthma in an allergy clinic population

Fractionated exhaled nitric oxide (FeNO) expression is increased in airway inflammation and several studies have suggested that FeNO measurement can be useful in patients with asthma. Atopic individuals have increased FeNO levels, indicating that atopy may be a codeterminant in FeNO production. The aim of this study was to determine the discriminative value of FeNO for asthma and other atopic conditions in the general allergy clinic. Patients referred to the outpatient allergy clinic were screened. A standardized questionnaire was taken and atopic status was assessed (skin-prick test or specific plasma IgE). FeNO level and spirometry were measured. If the patient's history was suspect for asthma, a provocative concentration causing a 20% decrease in forced expiratory volume in 1 second (PC(20)) histamine challenge followed. One hundred fourteen steroid-naive patients were included. Forty-two subjects were diagnosed as asthmatic patients and 72 were diagnosed as nonasthmatic patients, comprising patients with allergic rhinitis (n = 32), nonallergic rhinitis (n = 11), urticaria (n = 11), eczema (n = 7), and other (n = 11). Asthmatic patients had a higher FeNO level than nonasthmatic patients (44 ppb versus 17 ppb; p < 0.001). Receiver operating characteristic curve analysis revealed the optimal FeNO level to distinguish asthma from nonasthma at 27 ppb, with a sensitivity of 78%, specificity of 92%, a positive predictive value of 86%, and a negative predictive value of 87%. Increased FeNO was positively correlated with the presence of respiratory symptoms (p < 0.01), airflow reversibility (p < 0.001), total IgE (p < 0.001), and negatively correlated with PC(20) histamine (p = 0.019). Multivariate analysis revealed that atopy was not a significant predictor of FeNO in asthmatic patients. Measuring FeNO is a simple and useful test to differentiate new asthma patients from those with other atopic conditions in a general allergy clinic.

Nasal AMP and histamine challenge within and outside the pollen season in patients with seasonal allergic rhinitis

Nasal hyperreactivity is a prominent feature of allergic rhinitis. Variation in nasal hyperreactivity with different challenge agents in and out of the pollen season has not been examined. We sought to compare nasal hyperreactivity with different challenge agents before, during, and after the pollen season. Grass pollen-monosensitized patients performed cumulative-dose challenges with nasal AMP (25-800 mg · mL(-1)) and histamine (0.25-8 mg · mL(-1)) before, during, and after the grass pollen season. Outcomes included the provocative concentration of agent causing a 30% decrease in the peak nasal inspiratory flow (PNIF) (PC(30)), recovery profile, and diary cards. Nineteen participants completed per protocol. AMP PC(30) values for PNIF worsened by 1.33 (95% CI, 0.20-2.44; P = .02) doubling dilutions during the season but recovered after the season. The AMP recovery curve showed a -14.39% difference (95% CI, -21.11% to -7.66%; P < .001) during the season and remained abnormal after the season (-8.05% [95% CI, -14.78% to -1.33%; P < .05). Histamine PC(30) values did not change during the season, but recovery was prolonged by -14.47% (95% CI, -22.19% to -6.76%, P < .001), returning to baseline values after the season. Nasal symptoms, domiciliary PNIF, and serum eosinophil-derived neurotoxin levels returned to baseline values after the season. There is a reduction in AMP PC threshold but not histamine PC threshold during the pollen season, indicating that AMP is a more sensitive indicator of allergic inflammation. The residual hyperreactivity to nasal AMP, but not histamine, outside of the pollen season, seen as a persistently prolonged recovery curve, suggests the presence of primed airway mucosal mast cells, even in asymptomatic patients, and persistent activation of mediator pathways, such as cysteinyl leukotrienes.

Chronic cough and irritable larynx

Perennial rhinitis (PR), chronic rhinosinusitis (CRS), or both, asthma, and gastroesophageal reflux disease (GERD) are the most frequent triggers of chronic cough (CC). Extrathoracic airway receptors might be involved in all 3 conditions because asthma is often associated with PR/CRS and gastroesophageal refluxate might reach the upper airway. We previously found that most patients with rhinosinusitis, postnasal drip, and pharyngolaryngitis show laryngeal hyperresponsiveness (LHR; ie, vocal cord adduction on histamine challenge) that is consistent with an irritable larynx. We sought to evaluate the role of LHR in patients with CC. LHR and bronchial hyperresponsiveness (BHR) to histamine were assessed in 372 patients with CC and in 52 asthmatic control subjects without cough (asthma/CC-). In 172 patients the challenge was repeated after treatment for the underlying cause of cough. The primary trigger of CC was PR/CRS in 208 (56%) patients, asthma in 41 (11%) patients (asthma/CC+), GERD in 62 (17%) patients, and unexplained chronic cough (UNEX) in 61 (16%) patients. LHR prevalence was 76% in patients with PR/CRS, 77% in patients with GERD, 66% in patients with UNEX, 93% in asthma/CC+ patients, and 11% in asthma/CC- patients. Upper airway disease was found in most (95%) asthma/CC+ patients and in 6% of asthma/CC- patients. BHR discriminated asthmatic patients and atopy discriminated patients with PR/CRS from patients with GERD and UNEX. Absence of LHR discriminated asthmatic patients without cough. After treatment, LHR resolved in 63% of the patients and improved in 11%, and BHR resolved in 57% and improved in 18%. An irritable larynx is common in patients with CC and indicates upper airway involvement, whether from rhinitis/sinusitis, gastric reflux, or idiopathic sensory neuropathy.

P7 Occupational eosinophilic constrictive bronchiolitis with asthma in a foam cutter caused by Soya bean products

Introduction and backgroundSoya bean dust is a recognised cause of asthma. More recently Soya bean has bean used in the manufacture of foam. The main market for this ‘environmentally friendly...

Evaluation of histamine-induced conjunctival oedema in guinea pigs by means of image analysis

BackgroundConjunctival oedema is commonly observed in patients with allergic conjunctivitis and can be induced by histamine. In animal models of allergic conjunctivitis, conjunctival oedema is generally evaluated by measuring the...

Evaluation of optical rhinometry for nasal provocation testing in allergic and nonallergic subjects

Objective Optical rhinometry is a new method that quantifies light extinction in optical density to assess nasal blood volume as a measure of nasal patency. The purpose of this study is to evaluate optical rhinometry as an objective evaluation of nasal patency using nasal provocation testing with histamine and oxymetazoline. Study Design Prospective pilot. Setting Academic tertiary rhinologic practice. Subjects and Methods Convenience sample of five adult subjects with allergic rhinitis and five adult normal subjects who underwent challenge with histamine and oxymetazoline. Patients underwent challenge with increasing concentrations of histamine to determine the amount of histamine needed to cause a positive optical rhinometry reading. The same subjects then underwent histamine challenge with this amount followed by oxymetazoline. Nasal patency was assessed subjectively after each challenge with the visual analog scale. Results The median histamine amount needed to cause a positive response was statistically lower in allergic rhinitis as compared with nonallergic subjects at 150 μg and 300 μg, respectively ( P = 0.04). When comparing the optical rhinometry with subjective nasal congestion after histamine and oxymetazoline challenges, there was a statistically significant correlation with r = 0.79 ( P = 0.00003). Conclusion This initial study demonstrates a correlation between subjective symptoms of nasal patency and objective measurements with the optical rhinometer. Less histamine amount necessary to incite nasal congestion in allergic rhinitis suggests that these patients may be primed to the effects of histamine. These preliminary data suggest that optical rhinometry is able to assess changes in nasal patency during challenges with histamine and oxymetazoline.

Quality of life in adolescents with asthma, during the transition period from child to adult

The present investigation was designed to evaluate the health-related quality of life (HRQOL) of adolescents with asthma between the age of 16 and 21, when they are transferred from paediatric to adult care. In this prospective study, 156 teenagers (69 females) with asthma were screened employing spirometry, a histamine challenge, skin prick test for allergy and filled out the 'Living with Asthma Questionnaire' both at the time of entry into the study and after 2 and 5 years of follow-up. An exercise test and questions concerning regular performed exercise were carried out at baseline and 5 years later. At all three time-points, the HRQOL of the men was generally better than that of the women. At the same time, the HRQOL of both genders was significantly better, both in terms of the overall scores (P < 0.001) as well as the scores for most of the individual domains, in connection with the 5-year follow-up. The young women who exercised regularly at the time of their entry exhibited better HRQOL at this time than those who did not (P < 0.001), whereas regular exercise had no impact on the HRQOL of the young men. The women with severe asthma demonstrated a poorer HRQOL than those suffering from mild-to-moderate asthma. The HRQOL of adolescents with asthma improves with age. The pronounced positive correlation between regular exercise and HRQOL in female adolescents with asthma revealed here deserves special attention in the care of young women and deserves further exploration.

Airway responsiveness measured by barometric plethysmography in guinea pigs

Barometric plethysmography has become an increasingly used method to indirectly measure respiratory function in unrestrained freely-moving animals. This technique has been criticized because of physiological uncertainty of its major index, the enhanced pause (Penh). Moreover, a recent study raises concerns that during histamine challenges part of the Penh response could be produced by upper airways (nasal) responses. In this study we compared airway responsiveness measured by barometric plethysmography and total lung resistance (RL: ) in guinea pigs, and evaluated the role of upper airways during Penh measurement. Our results showed that intravenous acetylcholine or histamine caused a dose-dependent increase of the Penh values in non-anesthetized guinea pigs, which were correlated with RL: values obtained in separate groups of anesthetized animals. In anesthetized but spontaneously breathing guinea pigs intravenous acetylcholine or histamine also produced a dose-dependent increment of Penh, which was similar regardless if guinea pigs breathed through the nose or through a tracheal tube. Our results suggest that, independently of the physiological meaning of Penh, this index seems to be a useful indirect measurement for evaluating airway responsiveness to intravenous agonists in guinea pigs, and that nasal passage seems not to be involved in this measurement.

Effect of parenchymal stiffness on canine airway size with lung inflation.

Although airway patency is partially maintained by parenchymal tethering, this structural support is often ignored in many discussions of asthma. However, agonists that induce smooth muscle contraction also stiffen the parenchyma, so such parenchymal stiffening may serve as a defense mechanism to prevent airway narrowing or closure. To quantify this effect, specifically how changes in parenchymal stiffness alter airway size at different levels of lung inflation, in the present study, we devised a method to separate the effect of parenchymal stiffening from that of direct airway narrowing. Six anesthetized dogs were studied under four conditions: baseline, after whole lung aerosol histamine challenge, after local airway histamine challenge, and after complete relaxation of the airways. In each of these conditions, we used High resolution Computed Tomography to measure airway size and lung volume at five different airway pressures (0, 12, 25, 32, and 45 cm H2O). Parenchymal stiffening had a protective effect on airway narrowing, a fact that may be important in the airway response to deep inspiration in asthma. When the parenchyma was stiffened by whole lung aerosol histamine challenge, at every lung volume above FRC, the airways were larger than when they were directly challenged with histamine to the same initial constriction. These results show for the first time that a stiff parenchyma per se minimizes the airway narrowing that occurs with histamine challenge at any lung volume. Thus in clinical asthma, it is not simply increased airway smooth muscle contraction, but perhaps a lack of homogeneous parenchymal stiffening that contributes to the symptomatic airway hyperresponsiveness.

Bepotastine besilate, a highly selective histamine H 1 receptor antagonist, suppresses vascular hyperpermeability and eosinophil recruitment in in vitro and in vivo experimental allergic conjunctivitis models

To elucidate the ocular pharmacological properties of bepotastine besilate, a selective histamine H 1 receptor antagonist, when compared with other histamine H 1 receptor antagonists, using guinea pig allergic conjunctivitis models and in vitro models of eosinophil recruitment and mast cell membrane stabilization. Conjunctival vascular hyperpermeability was studied in guinea pigs passively sensitized with anti-ovalbumin antiserum or following subconjunctival injection of histamine. Modulation of eosinophil recruitment was evaluated for both platelet-activating factor (PAF)-induced eosinophil infiltration in guinea pigs and leukotriene B 4-induced in vitro chemotaxis of guinea pig peritoneal eosinophils. Membrane-stabilizing effects of bepotastine also were studied with rat peritoneal mast cells stimulated with the ionophore A23187. Histamine H 1 receptor antagonists including bepotastine besilate were topically administered before ovalbumin, histamine or PAF challenges for in vivo experiments or were added directly to mast cell and eosinophil medium in vitro. Bepotastine besilate significantly inhibited conjunctival vascular hyperpermeability in a dose-dependent manner with maximal effect for bepotastine besilate 1.5%. In separate in vivo experiments, bepotastine besilate 1.0% was significantly more effective than levocabastine 0.025% in the passive sensitization model or olopatadine 0.1% in the histamine-induced hyperpermeability model. Bepotastine besilate 1.0% further suppressed PAF-induced eosinophil infiltration into conjunctival tissue more effectively than ketotifen 0.05%. Chemotaxis of guinea pig peritoneal eosinophils and histamine release from rat peritoneal mast cells in vitro were also inhibited by addition of bepotastine. Olopatadine had a weak effect as compared to that of bepotastine on eosinophil chemotaxis and no effect on mast cell histamine release in our study conditions. Bepotastine besilate was more potent than olopatadine, ketotifen, or levocabastine in reducing vascular hyperpermeability in various animal models of allergic conjunctivitis. Mast cell function and eosinophil chemotaxis were also inhibited in vitro with bepotastine, suggesting bepotastine acts as an inhibitor of allergic response through multiple mechanisms: histamine H 1 receptor antagonism, mast cell stabilization, and inhibition of eosinophil migration to ocular inflammatory sites.

Repaired oesophageal atresia: respiratory morbidity and pulmonary function in adults

Although after oesophageal atresia (OA) repair in infancy, respiratory problems are common, their natural history remains unclear. We assessed morbidity, pulmonary function (PF), and bronchial hyperresponsiveness (BHR) in adults with repaired OA respiratory. 588 patients who underwent surgery for OA during 1947-1985 were identified and those 262 who were alive and had their native oesophagus were included. Respiratory symptoms and respiratory symptom-related quality of life (RSRQoL) were assessed by questionnaire and interview, and the patients underwent spirometry, a histamine challenge test, and an exhaled nitric oxide test. For the questionnaires, we added 287 carefully matched general population-derived controls. Among the 101 (58 male) patients, median age 36 yrs (range 22-56 yrs), respiratory morbidity was significantly increased compared to controls. Patients had more respiratory symptoms and infections, as well as asthma and allergies, and more often impaired RSRQoL (p<0.001 for all). PF tests revealed restrictive ventilatory defect in 21 (21%) patients, obstructive ventilatory defect in 21 (21%) patients, and both in 36 (36%) patients. A total of 41 (41%) had BHR, and in 15 (15%), it was consistent with asthma. The most significant risk factors for restrictive ventilatory defect were thoracotomy-induced rib fusions (OR 3.4, 95% CI 1.3-8.7; p = 0.01) and oesophageal epithelial metaplasia (OR 3.0, 95% CI 1.0-8.9; p = 0.05). After repair of OA, respiratory-related morbidity, restrictive ventilatory defect and BHR extended into adulthood. Nearly half the patients had BHR and over half had a restrictive ventilatory defect. Thoracotomy-induced rib fusions and gastro-oesophageal reflux-associated oesophageal epithelial metaplasia were the strongest risk factors for restrictive ventilatory defect.