Value of Bronchial Challenge in Scuba Diving Candidates

Bronchial challenges were effected with carbachol in 76 subjects who were candidates for a scuba diving group. Bronchial reactivity was assessed through airway resistance and forced expiratory volume in 1 sec (FEV₁) measurements. Medical interrogation had revealed symptoms of recent (RA) or ancient (AA) asthma, or allergic rhinitis (AL). Nearly half of the subjects (47%) presented bronchial hyperresponsiveness (BHR), which was much more frequent in the RA group, but whose strength did not depend on clinical presentation. Prevalence of BHR was fairly high (36%) in the AL group. BHR constituted a contraindication to scuba diving because it may promote pulmonary barotrauma.     

Bronchial hyperresponsiveness in an adult population in Helsinki: decreased FEV1, the main determinant

Introduction: Bronchial hyperresponsiveness (BHR) elevates the risk for development of respiratory symptoms and accelerates the decline in forced expiratory volume in the first second (FEV₁). We thus aimed to assess the prevalence, determinants and quantity of BHR in Helsinki. Objectives: This study involved 292 randomly selected subjects age 26–66 years, women comprising 58%. Methods: Following a structured interview, a spirometry, a bronchodilation test, and a skin‐prick test, we assessed a bronchial challenge test with inhaled histamine using a dosimetric tidal breathing method. Results included the provocative dose inducing a decrease in FEV₁ by 15% (PD₁₅FEV₁) and the dose‐response slope. For statistical risk factor‐analyses, the severity of BHR was considered; PD₁₅ values ≤1.6 mg (BHR) and ≤0.4 mg [moderate or severe BHR (BHR_ms)] served as cut‐off levels. Results: BHR presented in 21.2% and BHR_ms in 6.2% of the subjects. FEV₁ < 80% of predicted [odds ratio (OR) 4.09], airway obstruction (FEV₁/forced vital capacity < 88% of predicted) (OR 4.33) and history of respiratory infection at age <5 (OR 2.65) yielded an increased risk for BHR as ORs in multivariate analysis. For BHR_ms, the determinants were decreased FEV₁ below 80% of predicted (OR 27.18) and airway obstruction (OR 6.16). Respiratory symptoms and asthma medication showed a significant association with BHR. Conclusions: Of the adult population of Helsinki, 21% showed BHR to inhaled histamine. The main determinants were decreased FEV₁ and airway obstruction. Quantitative assessment of BHR by different cut‐off levels provides a tool for characterization of phenotypes of airway disorders in epidemiologic and clinical studies. Please cite this paper as: Juusela M, Pallasaho P, Sarna S, Piirilä P, Lundbäck B and Sovijärvi A. Bronchial hyperresponsiveness in an adult population in Helsinki: decreased FEV₁, the main determinant. Clin Respir J 2013; 7: 34–44.     

Decline of FEV1 in scuba divers

STUDY OBJECTIVES: Obstructive changes in lung function have been reported with cumulative scuba diving exposure. The aim of this study was to investigate the decline in FEV1 in scuba divers over time. DESIGN: Prospective controlled cohort study. SETTING: German Naval Medical Institute. PATIENTS: Four hundred sixty-eight healthy, male, military scuba divers and 122 submariners (control subjects) were entered. MEASUREMENTS AND RESULTS: Pulmonary function tests were performed in all subjects on at least three occasions with a minimum interval of 1 year between first and last measurement. The decline in FEV1 was investigated fitting a general linear model to FEV1 across time with a factorial main-effects model for slopes and intercepts with respect to the factors group, smoking status, and baseline FEV1. Mean baseline age of all subjects was 32 years (SD, 9.1), and mean body mass index was 24.7 kg/m2 (SD, 2.4). Subjects were followed up for 5 years (range, 1 to 9 years) on average. Baseline FEV1 exceeded the predicted values in both divers and nondiving control subjects. There was no significant difference in the decline of FEV1 between divers and control subjects. Over time, FEV1 declined more rapidly in smokers than in nonsmokers (p = 0.0064) and declined more rapidly also in subjects with a baseline FEV1 above average compared to subjects below average (p < 0.0001). The annual decline of FEV1 peaked in smoking divers who had a high FEV1 at baseline. CONCLUSIONS: The data indicate that scuba diving is not associated with an accelerated decline in FEV1. Combined exposure to diving and smoking contributes to the fall of FEV1; therefore, smoking cessation is advised for divers.     

Spontaneous changes in bronchial responsiveness in children and adolescents: an 18-month follow-up

The purpose of this study was to investigate spontaneous changes in bronchial responsiveness to inhaled histamine over a period of 18 months. The first measurements in 495 subjects, 7 to 16 years of age, were made in 1986. Bronchial hyperresponsiveness (BHR), i.e., PC-20 FEV1 less than or equal to 8.0 mg/mL, was found in 79 (16%) individuals, of whom 28 (35%) had symptoms of asthma. Twenty asthmatic and 42 non-asthmatic subjects who had BHR (78%) were re-examined 18 months later. The asthmatics had a modest change in BHR, while in the non-asthmatics bronchial response to inhaled histamine and exercise was significantly decreased. In twenty-two subjects (36%) bronchial response was within the normal range; of these 18 were non-asthmatic. Six asthmatics (30%) and two non-asthmatics (5%) had an increased BHR at follow-up. Two subjects (5%) developed symptoms of asthma by the time of follow-up, with an unchanged degree of BHR. Sex, age, atopic symptoms, and viral respiratory infections at the first examination were unrelated to changes in bronchial responsiveness. However, changes of BHR in the non-asthmatic subjects were significantly correlated to changes in bronchial response to exercise. Although spontaneous changes in bronchial responsiveness occur in asthmatic, as well as non-asthmatic subjects, asthmatics persistently have hyperresponsive airways. Development of asthma was found to occur among subjects with persistent BHR.     

Mediators in Exhaled Breath Condensate after Hypertonic Saline Challenge

Background. Airway narrowing after hypertonic saline challenge (HSC) is postulated to be mediated by bronchoconstrictors and inflammatory mediators. Objective. To study the mechanism of this challenge by using exhaled breath condensate (EBC). Methods. Fifty-six subjects (9 to 72 years of age) performed an HSC, with EBC collection and exhaled nitric oxide (FENO) measurements before and after the challenge. Bronchial hyper-reactivity (BHR) was defined if forced expiratory volume in 1 second (FEV₁) decreased by 10% compared with baseline (PD₁₀). EBC volume was recorded and was analyzed for mucin, histamine, nitrite/nitrate, and pH. Results. Those with BHR had a significant rise in EBC volume/5-minute collection period after challenge (286.3 ± 25.6 μl vs 402.2 ± 31.3 μl, p = 0.0002), while BHR(?) subjects did not show this change (387.6 ± 29.7 μl vs 364.1 ± 30.1 μl, p = 0.55). FENO showed a significant decrease in both BHR(+) and BHR(?) groups after challenge (p = < 0.0001). In BHR(+) subjects histamine increased significantly (1.3 ± 0.1 μM vs 1.5 ± 0.1 μM, p = 0.006) compared with baseline, while EBC pH and mucin increased significantly after HSC in both groups. EBC nitrite did not change in either group. Conclusion. EBC analysis suggests that HSC causes an increase in pH and mucin in both groups, but EBC volume and histamine only increased in the BHR(+) group. This suggests that mast cells are activated and fluid flux is associated with the positive response, while mucin release is independent of BHR in HSC.     

The interrelationship among bronchial hyperresponsiveness, the diagnosis of asthma, and asthma symptoms

Bronchial hyperresponsiveness (BHR) to inhaled histamine has often been cited as the gold standard in asthma diagnosis, but recently this has been questioned. This report assesses the relationship of BHR to asthma symptoms and asthma diagnosis in a large community-based sample of children. A total of 2,053 children 7 to 10 yr of age were randomly sampled from Auckland primary schools and assessed by a questionnaire and histamine inhalation challenge. In all, 14.3% had had asthma diagnosed, 29.6% reported having had one of the four respiratory symptoms in in the previous 12 months, and 15.9% had BHR (PD20 less than or equal to 7.8 mumol histamine). After a cumulative dose of 3.9 mumol histamine, the percent change in FEV1 from postsaline FEV1 was unimodally distributed, with those in whom asthma had been diagnosed dominating the severe end of the spectrum. However, 53% of those with BHR had no asthma diagnosis, and 41% had no current asthma symptoms. On the other hand, 48% of all subjects with diagnosed asthma and 42% of children with diagnosed asthma and current symptoms did not have BHR. Although severity of BHR tended to increase with wheezing frequency, all grades of severity (including no BHR) were found for any given frequency of wheeze. An existing diagnosis of asthma identified symptomatic children more accurately than did BHR, regardless of the criteria used for BHR or for "symptomatic" and irrespective of ethnic group. In conclusion, BHR is related to, but not identical to, clinical asthma. Bronchial challenge testing is an important tool of respiratory research, but cannot reliably or precisely separate asthmatics from nonasthmatics in the general community.     

Bronchial responsiveness to adenosine 5'-monophosphate (AMP) and methacholine differ in their relationship with airway allergy and baseline FEV(1)

Bronchial hyperresponsiveness (BHR) and inflammation are central hallmarks of asthma. Studies in patients with asthma suggest that BHR to adenosine 5'-monophosphate (AMP) is a better marker of bronchial inflammation than BHR to methacholine. The association between markers of airway inflammation and BHR to methacholine and AMP in a population of young adults, with mild symptoms if any, was evaluated. A total of 230 subjects who participated in a follow-up study on occupational allergy were included. Before exposure to occupational allergens, subjects completed a questionnaire on respiratory symptoms and were tested for atopy, blood eosinophilia (> or =275/mm(3)), and BHR to methacholine and AMP (> or =15% fall in FEV(1)). Risk estimates were expressed as prevalence ratios (PR) and 95% confidence intervals (95% CI). Dose-response slopes (DRS) for methacholine and AMP were compared between healthy control subjects, self-reported allergic rhinitis, and allergic asthma. BHR to AMP was associated with allergic rhinitis (PR 2.51, 95% CI: 1.22;5.17), allergic asthma (PR 4.38, 95% CI: 1.98;9.66), with atopy (PR 3.87, 95% CI: 1.76;8.52), and blood eosinophilia (PR 3.57, 95% CI: 1.48;8.77), but not with baseline FEV(1). BHR to methacholine was inversely related to prechallenge FEV(1) (PR 0.97, 95% CI: 0.96;0.99). For both methacholine and AMP the geometric mean DRS increased along the axis asymptomatic-allergic rhinitis-allergic asthma, but for AMP the increase was the strongest. In this population study among young adults, BHR to AMP refers to allergic background of airway lability and BHR to methacholine is related to a diminished airway caliber.     

Exhaled Nitric Oxide in Children with Allergic Rhinitis and/or Asthma: A Relationship with Bronchial Hyperreactivity

Background. Nowadays, the measure of the fractional concentration of exhaled nitric oxide (FeNO) enables to assess airway inflammation during an office visit and there is international consensus on this testing methodology. The aim of this study was to evaluate whether FeNO measurement is predictable for bronchial hyperreactivity (BHR) in children with allergic rhinitis, asthma, or both. Methods. Two hundred and eighty children with allergic rhinitis, allergic asthma, or both were evaluated. Bronchial function (FEV₁ and FEF_25–75), BHR (assessed by methacholine challenge), FeNO, and sensitizations were assessed. Results. Bronchial function, BHR, and FeNO were significantly different in the three groups (p < .001). A strong inverse correlation between FeNO and BHR was found in patients with asthma and with asthma and rhinitis (r?=??0.63 and r?=??0.61, respectively). A cutoff of 32 ppb of FeNO was a predictive factor for BHR. Conclusions. This study highlights the relevance of FeNO as possible marker for BHR in allergic children and underlines the close link between upper and lower airways.     

Bronchial Sensitivity to Histamine in Former Asthmatics: Redevelopment of Symptoms During a Year of Followup

The aim of this protocol was to study bronchial responsiveness in 23 former asthmatics who were free of symptoms for at least 5 years. Bronchial hyperreactivity (BHR) was evaluated with histamine challenge test and the results were compared with those of 20 normal subjects and 20 current asthmatic patients. Among the former asthmatics 65% fulfilled the criteria of BHR. During 1 year of followup, two former asthmatics redeveloped asthma symptoms. Interestingly, one patient had no BHR when initially tested. These findings suggest that the absence of BHR does not guarantee the nonrecurrence of asthma symptoms in former asthmatics.     

Tauchen und Herz

Diving with self-contained underwater breathing apparatus (scuba) has become a popular recreational sports activity throughout the world. A high prevalence of cardiovascular disorders among the population makes it therefore likely that subjects suffering from cardiovascular problems may want to start scuba diving. Although scuba diving is not a competitive sport requiring athletic health conditions, a certain medical fitness is recommended because of the physical peculiarities of the underwater environment. Immersion alone will increase cardiac preload by central blood pooling with a rise in both cardiac output and blood pressure, counteracted by increased diuresis. Exposure to cold and increased oxygen partial pressure during scuba diving will additionally increase afterload by vasoconstrictive effects and may exert bradyarryhthmias in combination with breath-holds. Volumes of gas-filled body cavities will be affected by changing pressure (Figure 1), and inert gas components of the breathing gas mixture such as nitrogen in case of air breathing will dissolve in body tissues and venous blood with increasing alveolar inert gas pressure. During decompression a free gas phase may form in supersaturated tissues, resulting in the generation of inert gas microbubbles that are eliminated by the venous return to the lungs under normal circumstances. Certain cardiovascular conditions may have an impact on these physiological changes and pose the subject at risk of suffering adverse events from scuba diving. Arterial hypertension may be aggravated by underwater exercise and immersion. Symptomatic coronary artery disease and symptomatic heart rhythm disorders preclude diving. The occurrence of ventricular extrasystoles according to Lown classes I and II, and the presence of atrial fibrillation are considered relative contraindications in the absence of an aggravation following exercise. Asymptomatic subjects with Wolff-Parkinson-White syndrome may be allowed to dive, but in case of paroxysmal supraventricular tachycardia they must refrain from diving. Pacemakers will fail with increasing pressure, but some manufacturers have proven their products safe for pressure equivalents of up to 30 m of seawater, so that patients may dive uneventfully when staying within the 0-20 m depth range. Significant aortic or mitral valve stenosis will preclude diving, whereas regurgitation only will not be a problem. Right-to-left shunts have increasingly gained attention in diving medicine, since they may allow venous gas microbubbles to spill over to the arterial side of the circulation enabling the possibility of arterial gas embolism. Significant shunts thus preclude diving. The highly prevalent patent foramen ovale is considered a relative contraindication only when following certain recommendations for safe diving (Table 2). Metabolic disorders are of concern, since adiposity is associated with both, higher bubble grades in Doppler ultrasound detection after scuba dives when compared to normal subjects, and an increased epidemiologic risk of suffering from decompression illness. In conclusion, cardiovascular aspects are important in the assessment of fitness to dive, and certain cardiovascular conditions preclude scuba diving. Any history of cardiac disease or abnormalities detected during the routine medical examination should prompt to further evaluation and specialist referral.     

Analysis of factors associated with bronchial hyperreactivity to methacholine in bronchiectasis

Nonspecific bronchial hyperreactivity (BHR) has been reported to occur in patients with bronchiectasis. To evaluate this further, we studied 77 patients with stable bronchiectasis (noncystic fibrosis) with special reference to the prevalence of BHR to methacholine (MCh), and its relation to lung function, sputum characteristics, concommitant asthma, and atopy. The concentration of MCh required to produce a fall of 20% in forced expiratory volume in 1 s (FEV₁), PC₂₀, was determined by Wright’s nebulization tidal breathing method. BHR defined by a PC₂₀ ≤ 8 mg/ml was found in 21 of 47 (45%) subjects who underwent bronchial challenge. Presence of BHR was positively associated with low baseline spirometric values, diagnosis of asthma, long duration of disease, and elevated total IgE on univariant analysis, and was significantly related to FEV₁/forced vital capacity (FVC) ratio and asthma on multiple regression analysis. Ten of the 21 hyperreactive subjects did not have clinical asthma, whereas all 11 of 22 subjects with clinical asthma who underwent bronchial challenge were hyperreactive. Among those with BHR, there was a positive correlation between PC₂₀ and baseline FEV₁. When patients were further classified into asthmatic and nonasthmatic subjects, a positive correlation between PC₂₀ and FEV₁ was seen only in those without asthma. Frequency of infective episodes and inflammatory score of sputum assessed by average daily volume, purulence, and leukocyte count did not differ significantly in the groups with and without BHR. These results suggest that BHR in patients with bronchiectasis is associated with coexistent asthma and worse spriometric values, and not with the severity of bronchial sepsis. An erratum to this article is available at .     

Bronchial hyperreactivity in patients with mitral stenosis before and after successful percutaneous mitral balloon valvulotomy

OBJECTIVES: We aimed to identify the bronchial response to inhaled methacholine in patients with mitral stenosis (MS) and to clarify whether or not the bronchial hyperreactivity (BHR) is reversible after percutaneous mitral balloon valvulotomy (PBMV). PATIENTS AND SETTING: Thirty patients with MS and 28 age-matched healthy control subjects were prospectively evaluated with pulmonary function tests and methacholine challenge. The productive concentration of methacholine causing 20% decrease in FEV(1) (PC(20)) was calculated and used as a parameter of bronchial responsiveness. BHR was defined as a PC(20) < 8 mg/mL. Mean pulmonary artery pressure (PAP) and mean pulmonary capillary wedge pressure (PCWP) were recorded in all patients through a Swan-Ganz balloon-tipped catheter. Sixteen patients underwent PMBV, and a methacholine test was repeated after each procedure. RESULTS: Bronchial response to methacholine was significantly increased in patients with MS, so that 53% of them had BHR, whereas all control subjects were nonresponders. The PC(20) was closely correlated with the PAP (r = - 0.777; p < 0.001), PCWP (r = - 0.723; p < 0.001), and mitral valve area (MVA; r = 0.676; p < 0. 001). Balloon valvulotomy was successfully performed in all of the 16 patients, and the cardiac parameters (MVA, PAP, and PCWP) significantly improved after the procedure. In contrast, no significant changes were shown in pulmonary function test variables (total lung capacity, vital capacity [VC], FEV(1), and FEV(1)/VC). Although significant improvement was observed in the mean PC(20) values (from 4.97 +/- 5.24 to 7.47 +/- 6.96 mg/mL; p = 0.0006), BHR was completely eliminated in only one patient. CONCLUSIONS: Our data shows that BHR is fairly common among patients with MS, and severity of bronchial responsiveness is significantly correlated with the severity of MS. Moreover, PMBV leads to significant reduction in pulmonary congestion and a consequent improvement in BHR.     

Prevalence and nature of bronchial hyperresponsiveness in subjects with chronic obstructive pulmonary disease

The prevalence, nature, and severity of bronchial hyperresponsiveness in subjects with chronic obstructive pulmonary disease (COPD) is not known. To determine these factors, a 1 in 4 random sample of adults attending the Busselton population survey was studied. Subjects answered a modified Medical Research Council questionnaire and had spirometric function tested. They were defined as having COPD or asthma from the questionnaire. Bronchial responsiveness to histamine was measured using the rapid method, and results in the subjects with COPD were compared with those in asthmatic subjects with abnormal lung function. Fifty-nine subjects with COPD had a histamine inhalation test, and of these, 27 had bronchial hyperresponsiveness (BHR) (PD20FEV1 less than 3.9 mumol). The position of the dose response curves of the subjects with COPD overlapped considerably with those obtained from the 17 asthmatics. The geometric mean values for PD20FEV1 for these 2 groups were significantly different (p less than 0.001). There was a good correlation between FEV1/FVC and PD20FEV1 values in the subjects with COPD but not in the asthmatic subjects. Pretreatment with 600 micrograms of aerosolized fenoterol significantly improved the PD20FEV1 values in 11 subjects with COPD (1.26 to 6.16 mumol; p less than 0.001). The results suggest that approximately half the subjects with COPD in a general population have BHR but this BHR has different characteristics from that occurring in asthmatic subjects.     

Atopic Status and Level of Bronchial Responsiveness in Parents of Children with Acute Bronchiolitis

To examine whether children with a genetic predisposition to asthma are more likely to be afflicted with bronchiolitis, we studied 122 parents of infants who were hospitalized with the diagnosis of acute bronchiolitis (index group) and 120 parents of children who had never suffered from this disease (control group). The parents underwent bronchial challenge testing with methacholine and skin prick testing with common airborne allergens, and gave blood specimens for measurement of serum total IgE. There was no difference in atopic status, as assessed by the prevalence of atopy (at least one positive response to the allergens tested) or by serum total IgE levels, between index and control parents. The prevalence of bronchial hyperresponsiveness (BHR) (concentration of methacholine causing a 20% reduction in forced expiratory volume in 1 sec [PC₂₀] < 18 mg/mL) was higher in index parents than in control parents (17.2% vs. 7.5%, p = 0.02). Bronchial responsiveness (BR) index was significantly higher in index parents than in control parents (1.135 ± 0.088 vs. 1.104 ± 0.071, p < 0.01). Parents of children who were hospitalized with acute bronchiolitis showed a higher level of BR, but not atopy. This suggests that in terms of BHR, there may be a genetic predisposition to the development of bronchiolitis.     

Blood glucose changes and adjustments of diet and insulin doses in type 1 diabetic patients during scuba diving (for a change in French regulations)

OBJECTIVE: In France, diabetic subjects were not allowed to dive. The principal risk is hypoglycemia during immersion. However scuba diving is allowed in many countries. To follow blood glucose changes, food intake and insulin adjustments in type 1 diabetic patients when diving, and to propose specific guidelines for such patients willing to practice recreational scuba diving. METHODS: Fifteen well-controlled (mean HbA1c: 7.2%) type 1 diabetic patients without complications were volunteer to dive under strict medical monitoring. They dove 8 times in 4 days in autumn at a depth of 20 meters, in 12 degrees C to 16 degrees C water. A strict protocol based on blood glucose was implemented to prevent hypoglycaemia. RESULTS: No case of hypoglycemia was observed and no faintness was reported underwater. Mean blood glucose before diving was 200 mg/dl (11 mmol/l). There was a mean fall in blood glucose of 40 mg/dl (2.2 mmol/l) during dives, a mean decrease in daily insulin doses by 19.3% on the last day. Daily energy intake was 3,225 Kcal in average. A continuous glucose monitoring (CGMS) was performed in one patient and showed a rather stable glycemia during immersion but a decrease within the 8 hours after. CONCLUSION: When respecting a strict protocol to prevent hypoglycaemia, the risk of hypoglycaemia appears quite low. We recommend an ideal glycemic goal of 200-250 mg/dl (11-13.75 mmol/l) before immersion, a higher reduction of insulin doses (-30%) and taking carbohydrates on board in any case. The present data have recently led the French diving federation (FESSM) to allow type 1 diabetic patients to dive with some restrictive qualification requirements: dives within the "safety curve" (no decompression curve), in above 14 degrees C water, depth limited to the median space range (6 to 20 meters), plus mandatory guidance by a diving instructor.     

Scuba diving is possible and safe for patients with haemophilia

Summary. For a long time, physical activities have been contraindicated in haemophiliacs or were restricted to few activities. Sports are nowadays advocated for haemophiliacs. Although various lists of physical activities have been proposed, scuba diving is never mentioned. Thus, with a group of haemophilic volunteers, a study was launched on whether, with strict medical follow‐up, scuba diving could be allowed for patients with haemophilia. All the participants followed a training program including theory and assessment. In 6 years, a total of 517 dives were performed by 20 patients with congenital bleeding disorders. Nine were under prophylaxis for haemophilia, and nine received on‐demand treatment. Two patients had type I von Willebrand’s disease. Among the 20 patients, 12 made 12–153 dives, whereas six made eight dives each. No incident was noted during or after the dives. Thus, scuba diving can be authorized for PWH, if they have none of the specific medical contraindications for diving and if they have received medical training allowing them to manage their disease themselves.     

Bronchial hyperresponsiveness to methacholine in patients with primary Sj?gren's syndrome.

The prevalence of bronchial hyperresponsiveness (BHR) to methacholine inhalation in a consecutive series of 21 patients with primary Sjögren''s syndrome was studied prospectively. Slight to severe BHR was seen in 12/20 (60%) of the patients. Ten of 12 patients with BHR (83%) had a non-productive cough, wheezing, or intermittent breathlessness. Bronchial hyperresponsiveness was more common in patients with extraglandular symptoms (10/14, 71%) than in those with only glandular symptoms (29%). Spirometrically 29% (6/21) of the patients had ''small airways'' disease'', and all those had BHR. Of 6/21 (29%) who had diffuse interstitial lung disease, two had BHR. Three of the four patients with obstructive lung function were challenged with methacholine and two of them had BHR. Only two patients with BHR had normal spirometry findings. The data showed that respiratory disease--mostly mild or moderate but even severe bronchial hyperresponsiveness--is commonly seen in patients with primary Sjögren''s syndrome.     

Sputum eosinophilia and bronchial responsiveness in patients with chronic non-productive cough responsive to anti-asthma therapy

OBJECTIVE: We aimed to examine airway inflammation and bronchial responsiveness in patients with chronic non-productive cough responsive to anti-asthma therapy. METHODOLOGY: Bronchial responsiveness to methacholine as well as the number of inflammatory cells and concentration of eosinophil cationic protein (ECP) in induced sputum were measured in 42 patients with chronic non-productive cough of unknown origin. Their response to bronchodilator, antiallergic and inhaled or oral glucocorticoid therapy was subsequently assessed. RESULTS: Complete remission of coughing was attained with anti-asthma therapies in 34 patients (responder group), while eight patients did not respond (non-responder group). Twenty patients in the responder group and three in the non-responder group showed bronchial hyperresponsiveness (BHR). The number of eosinophils and ECP levels in the sputum from responders with BHR were significantly increased when compared with those from non-responders and healthy subjects. These sputum measures were also significantly increased in responders without BHR when compared with healthy subjects. However, there were no significant differences in these inflammatory markers between the responders with and without BHR. The neutrophil numbers in the sputum from non-responders and responders both with and without BHR were also significantly higher than in control subjects, but there were no significant differences. CONCLUSIONS: These findings suggest that patients with chronic non-productive cough responsive to anti-asthma therapy characteristically have eosinophilic airway inflammation, which may play an important role in the development of chronic cough. Furthermore, the evaluation of not only bronchial responsiveness but also airway inflammation by examination of induced sputum may be useful for diagnosis and deciding on therapeutic strategies.     

Bronchial Responsiveness to Dry Air Hyperventilation in Smokers May Predict Decline in Airway Status Using Indirect Methods

Background

Disabling respiratory symptoms and rapid decline of lung function may occur in susceptible tobacco smokers. Bronchial hyperresponsiveness (BHR) elicited by direct challenge methods predicts worse lung function outcomes. The aim of this study was to evaluate whether BHR to isocapnic hyperventilation of dry air (IHDA) was associated with rapid deterioration in airway status and respiratory symptoms.

Methods

One hundred twenty-eight smokers and 26 age- and sex-matched healthy individuals with no history of smoking were investigated. All subjects completed a questionnaire. Spirometry and impulse oscillometry (IOS) measurements were recorded before and after 4 min of IHDA. The tests were repeated after 3 years in 102 smokers and 11 controls.

Results

Eighty-five smokers (66 %) responded to the challenge with a ≥2.4-Hz increase in resonant frequency (F _res), the cutoff limit defining BHR, as recorded by IOS. They had higher F _res at baseline compared to nonresponding smokers [12.8 ± 3.2 vs. 11.5 ± 3.4 Hz (p < 0.05)] and lower FEV₁ [83 ± 13 vs. 89 ± 13 % predicted (p < 0.05)]. Multivariable logistic regression analysis indicated that wheezing (odds ratio = 3.7, p < 0.01) and coughing (odds ratio = 8.1, p < 0.05) were significantly associated with hyperresponsiveness. An increase in F _res was recorded after 3 years in responding smokers but not in nonresponders or controls. The difference remained when subjects with COPD were excluded.

Conclusions

The proportion of hyperresponsive smokers was unexpectedly high and there was a close association between wheezing and coughing and BHR. Only BHR could discriminate smokers with rapid deterioration of airway status from others.     

Allergic rhinitis and onset of bronchial hyperresponsiveness: a population-based study

RATIONALE: Patients with allergic rhinitis have more frequent bronchial hyperresponsiveness (BHR) in cross-sectional studies. OBJECTIVES: To estimate the changes in BHR in nonasthmatic subjects with and without allergic rhinitis during a 9-year period. METHODS: BHR onset was studied in 3,719 subjects without BHR at baseline, who participated in the follow-up of the European Community Respiratory Health Survey. MEASUREMENTS AND MAIN RESULTS: BHR was defined as a >or=20% decrease in FEV(1) for a maximum dose of 1 mg of methacholine. Allergic rhinitis was defined as having a history of nasal allergy and positive specific IgE (>or=0.35 IU/ml) to pollen, cat, mites, or Cladosporium. The cumulative incidence of BHR was 9.7% in subjects with allergic rhinitis and 7.0% in subjects with atopy but no rhinitis, compared with 5.5% in subjects without allergic rhinitis and atopy (respective odds ratios [OR] and their 95% confidence intervals [95% CI] for BHR onset, 2.44 [1.73-3.45]; and 1.35 [0.86-2.11], after adjustment for potential confounders including sex, smoking, body mass index and FEV(1)). Subjects with rhinitis sensitized exclusively to cat or to mites were particularly at increased risk of developing BHR (ORs [95% CI], 7.90 [3.48-17.93] and 2.84 [1.36-5.93], respectively). Conversely, in subjects with BHR at baseline (n = 372), 35.3% of those with allergic rhinitis, compared with 51.8% of those without rhinitis had no more BHR at follow-up (OR [95% CI], 0.51 [0.33-0.78]). BHR "remission" was more frequent in patients with rhinitis treated by nasal steroids than in those not treated (OR [95% CI], 0.33 [0.14-0.75]). CONCLUSIONS: Allergic rhinitis was associated with increased onset of BHR, and less chance for remission except in those treated for rhinitis.