Biomedical subjects

H Turcotte

Publications and source records attributed to H Turcotte.

At least 19 recordsLinked to original sources

PubMed2003

Variability of inflammatory cell counts on bronchial biopsies of normal subjects.

Bronchial biopsies are currently used to study the pathophysiology of airway diseases, and comparisons are often made with biopsies from healthy volunteers. It is therefore important to evaluate the variability in each parameter analyzed in bronchial biopsies of healthy volunteers in order to be able to discriminate significant changes. We analyzed bronchial biopsies of 31 nonsmoking, nonatopic healthy subjects who volunteered as normal controls for studies on pathophysiology of asthma. Mean % epithelial desquamation was 23.7% of observed total epithelial length. No subepithelial fibrosis was observed. Inflammatory cell counts (/mm(2) connective tissue surface) were variable among subjects but not different between small (<or=0.25 mm(2)) and large biopsies. Medians (range) of positive cells were for CD3: 20.5 (0-530.0), CD4: 6.2 (0-124.4), CD8: 1.8 (0-81.5), CD25: 0 (0-62.3), HLA-DR: 80.0 (3.5-524.2), EG1: 5.3 (0-180.6), EG2: 6.4 (0-48.8), AA1: 51.3 (0-286.4), CD45: 39.7 (0-448.5) and CD45ro: 28.6 (0-425.2). Subjects living in an urban area had significantly higher CD8-positive cell counts than those from suburban areas ( p = 0.0001). The presence of an animal at home was associated with lower positive cell counts for CD4 ( p = 0.02), CD45 ( p = 0.02) and HLA-DR ( p = 0.01). In conclusion, the variability in the number and expression of markers of activity of bronchial immune cells in normal subjects likely reflects variable host responses to environmental exposures and must be taken into account when compared to specimens obtained in subjects with airway diseases.

Adolescent↗

PubMed2003

Airway inflammation in asthma with incomplete reversibility of airflow obstruction.

This study aimed to determine whether there is a persistent or different type of airway inflammation in patients with an incomplete reversibility of airflow obstruction (IRAO) despite optimal treatment and if so, whether it is associated with an accelerated decline of pulmonary function. Fifteen asthmatic patients with IRAO, and 23 with complete reversibility of airflow obstruction (CRAO) had a spirometry and an induced-sputum (IS) analysis. Past FEV1 values were recorded over 2-12 years during periods of stable asthma. Medians (range) for IS cell differentials were: lymphocytes, 0(0-3)/1(0-2)%; neutrophils, 56(13-88)/38(3-84)% and eosinophils, 2.0(0-82)/4.0(0-68)%, (all P>0.05). Among non-smoking patients, those with IRAO had more neutrophils in IS than those with CRAO (P=0.019). Mean (+/-SEM) yearly fall in FEV1 in IRAO or CRAO patients was 54+/-21/84+/-16 ml/year (P>0.05, predicted age-related decline < or = 26 ml/year, P=0.0008). In the whole group of asthmatic patients, decline of FEV1/year was inversely correlated with the % neutrophils in sputum (r(s)=-0.436, P=0.008) and, in IRAO patients, with the duration of asthma (r(s)=-0.559, P=0.037). In conclusion, persistent airway inflammation and increased decline in pulmonary function can be observed in both asthmatic patients with IRAO/CRAO and are of similar magnitude. Non-smoking patients with IRAO had more neutrophils in IS than CRAO.

Adrenal Cortex Hormones↗

PubMed2001

Electrocardiographic findings in athletes: the prevalence of left ventricular hypertrophy and conduction defects.

OBJECTIVES: To determine whether there are electrocardiographic differences or distinctive abnormalities between athletes and sedentary subjects, and to verify the relationship between vagal activity measured by heart rate variability (SD of all normal-to-normal intervals [SDNN]) and possible electrocardiographic abnormalities. SUBJECTS AND METHODS: Resting electrocardiograms and heart rate variability measurements were performed separately during a single visit on 100 athletes and 50 nonathlete control subjects aged 18 to 55 years. The athletes were from the following various sports disciplines: long-distance running, mountain biking, cross-country skiing, biathlon, speed skating, swimming and triathlon. RESULTS AND CONCLUSIONS: There were significantly longer RR intervals, PR intervals and QT intervals in athletes than in control subjects (all P<0.05). The QRS complex and QTc did not show significant differences (both P>0.05). The prevalence of left ventricular hypertrophy (LVH) and incomplete right bundle branch block (IRBBB) was 10% and 7%, respectively, in athletes, but these conditions were absent in control subjects; among athletes, 2% presented with both conditions. LVH and IRBBB were more common among long-distance runners (six of 14 and four of 14, respectively) and could be attributed to normal, long term adaptation to intense, repeated exercise. LVH was related to age (P=0.04), whereas IRBBB was influenced by the number of years of training in the respective sports discipline (P=0.03). The mean SDNN value was significantly more elevated in athletes (P=0.0001), reflecting a higher parasympathetic tone than in sedentary control subjects. However, there was no relationship between vagal activity and LVH or IRBBB (both P>0.05).

Adolescent↗

PubMed2000

Influence of sympatho-vagal balance on airway responsiveness in athletes.

The increased prevalence of airway hyperresponsiveness (AHR) observed among athletes suggests that high-level training may contribute to the development of AHR. We investigated the possible influence of the sympatho-vagal balance on this phenomenon in 40 athletes and 10 sedentary controls. Each subject filled out a respiratory questionnaire, had a methacholine challenge, and measurements were made of their baseline plasma catecholamines [epinephrine (E), norepinephrine (NE) and dopamine (DA)] as a reflection of sympathetic tone, and their heart rate variability (SDNN: standard deviation of all normal-to-normal intervals) as an indicator of parasympathetic tone. The athletes had a 45% prevalence of AHR (defined as PC20 < 16 mg/ml, where PC20 is the concentration of methacholine inducing a 20% fall in the forced expiratory volume in 1 s, FEV1) with a mean PC20 of 21.2 mg/ml compared with 10% prevalence (mean PC20: 74.4 mg/ml) in sedentary subjects (P < 0.01). Plasma catecholamine values were not significantly different between the two groups (all P > 0.05), but the estimated parasympathetic tone was higher in athletes (P = 0.01). When data from all subjects were analyzed together, plasma E and NE correlated with PC20 (r = 0.39, P = 0.005 and r = 0.29, P < 0.005) but DA and SDNN did not (both P > 0.05). However, the ratios E/SDNN, NE/SDNN and DA/SDNN showed significant correlations with PC20 (r = 0.42, P < 0.01; r = 0.33, P < 0.005 and r = 0.31, P < 0.05, respectively) This study suggests that the sympatho-vagal balance may contribute to the increased AHR in the population studied but this influence alone cannot explain the higher prevalence of AHR in athletes.

Adult↗

PubMed2000

Asthma and airway hyper-responsiveness in adults who required hospital admission for bronchiolitis in early childhood.

Viral respiratory infections in infancy may contribute to the development of airway hyper-responsiveness (AHR) in childhood but their effects on respiratory function at the adult age are still uncertain. A group of 42 subjects aged 17-35 with a pediatrician-made diagnosis of severe bronchiolitis in infancy (Br) were compared for the presence of asthma and AHR to a control group (C) paired for age and gender, without evidence of lower respiratory disease in infancy. All had a respiratory and environmental questionnaire, allergy skin prick tests, blood eosinophil count, total serum IgE determination and measurements of expiratory flows and airway response to methacholine. In Br and C groups, respectively, 38 and 12% of subjects had a physician-made diagnosis of asthma, 26 and 7% used bronchodilators and 12 and 0% an inhaled corticosteroid; 71 and 67%, respectively, were atopic, 50 and 24% were smokers and 43 and 17% had a first-degree relative with asthma. Mean baseline FEV1 and FEV1/FVC ratio were lower in the Br than in the C group, with 94/103% (P=0.002) and 80/87 (P<0.0001) of the predicted value, respectively. Geometric mean PC20 methacholine was significantly lower in the Br than in the C group 3.9/20.3 mg ml(-1) (P<0.0001). Mean blood eosinophil count and serum IgE levels were similar in both groups (P> 0.05). In conclusion, asthma and AHR were found more frequently in young adults with a past history of bronchiolitis, suggesting that this type of respiratory infection may contribute to altered pulmonary function in adulthood, although it may also represent an early manifestation of asthma. The influence of potential confounding factors, such as familial predisposition and exposure to cigarette smoke on the development of asthma and AHR in the Br group, cannot be excluded.

Adolescent↗

PubMed2000

Cytokine expression in the lower airways of nonasthmatic subjects with allergic rhinitis: influence of natural allergen exposure.

BACKGROUND: Natural exposure to pollen provokes an increase in airway responsiveness in nonasthmatic subjects with seasonal allergic rhinitis. This natural exposure may induce inflammatory cell recruitment and cytokine release, leading to lower airway inflammation. OBJECTIVE: The aim of this study was to characterize lower airway inflammation in nonasthmatic pollen-sensitive subjects. METHODS: We performed immunohistochemical tests on bronchial biopsy specimens from subjects with rhinitis who had no past or current history of asthma to evaluate cytokine expression and inflammatory cell numbers and activation both in and out of the pollen season. RESULTS: The number of CD4(+), CD8(+), and CD45RO(+) lymphocyte subpopulations were significantly higher during the pollen season compared with the out-of-season period (P <.04). Furthermore, EG1(+) cells tended to increase after natural pollen exposure (P =.06). The number of IL-5(+) cells increased significantly after natural exposure to pollen compared with out-of-season numbers (P <.01). This increase in IL-5 expression was correlated with the numbers of CD3(+), CD4(+), CD45RO(+), and EG1(+) cells. The numbers of tryptase-positive, IFN-gamma(+), and IL-4(+) cells did not change after natural exposure. CONCLUSION: This study showed that natural pollen exposure was associated with an increase in lymphocyte numbers, eosinophil recruitment, and IL-5 expression in the bronchial mucosa of nonasthmatic subjects with allergic rhinitis.

Adult↗

PubMed2000

Airway hyperresponsiveness in elite athletes.

It has been suggested that high-level training could contribute to the development of airway hyperresponsiveness (AHR), but the comparative effects of different sports on airway function remains to be determined. We evaluated 150 nonsmoking volunteers 18 to 55 yr of age; 100 athletes divided into four subgroups of 25 subjects each according to the predominant estimated hydrocaloric characteristic of ambient air inhaled during training: dry air (DA), cold air (CA), humid air (HA) and a mixture of dry and humid air (MA), and 50 sedentary subjects. Each subject had a respiratory questionnaire, a methacholine challenge, allergy skin-prick tests, and heart rate variability recording for evaluation of parasympathetic tone. The athletes had a 49% prevalence of AHR (PC(20) < 16 mg/ml), with a mean PC(20) of 16.9 mg/ml, compared with 28% (PC(20): 35.4) in sedentary subjects (p = 0.009). The prevalence (%) of AHR and mean PC(20) (mg/ml) varied as followed in the four subgroups of athletes: DA: 32% and 30.9; CA: 52% and 15.8; HA: 76% and 7.3; and MA: 32% and 21.5 (p = 0.002). The estimated parasympathetic tone was higher in athletes (p < 0.001), but this parameter showed only a weak correlation with PC(20) (r = -0.17, p = 0.04). This study has shown a significantly higher prevalence of AHR in athletes than in the control group because of the higher prevalence in the CA and HA groups. Parasympathetic activity may act as modulator of airway responsiveness, but the increased prevalence of AHR in our athlete population may be related to the type and possibly the content of inhaled air during training.

Adolescent↗

PubMed2000

Airway hyperresponsiveness, inflammation, and subepithelial collagen deposition in recently diagnosed versus long-standing mild asthma. Influence of inhaled corticosteroids.

This study aimed at documenting airway inflammation and subepithelial collagen deposition in patients using only inhaled beta(2)-agonists with either recently diagnosed asthma (RDA: </= 2 yr, n = 16) or long-standing asthma (LSA: >/= 13 yr, n = 16) and at the influence of an intense inhaled corticosteroid (ICS) treatment on these parameters, in relation to changes in airway responsiveness. Patients had a methacholine inhalation test and a bronchoscopy with bronchial biopsies before and after an 8-wk treatment with inhaled fluticasone propionate (FP), 1,000 microgram/day. Baseline FEV(1) (mean +/- SEM) was normal and similar in both groups (RDA: 98.1 +/- 2.7, LSA: 94.5 +/- 4.6%). Geometric mean methacholine PC(20) was lower in LSA than in RDA (0.44 versus 3.37 mg/ml) at baseline and improved similarly by 1.85 and 1.86 double concentrations with FP treatment. PC(20) normalized (>/= 16 mg/ml) in five patients with RDA and two patients with LSA. Baseline mean bronchial cell counts (per mm(2) connective tissue surface) for CD3(+), CD4(+), CD8(+), CD25(+), EG1(+), CD45ro(+), and AA1(+) cells were similar in both groups. With FP, EG1(+) (p < 0.001), EG2(+) (p = 0.018), and AA1(+) counts (p = 0.009) decreased significantly in both groups while CD45ro(+) (p = 0.02) counts decreased only in LSA. Baseline type 1 and type 3 collagen deposition underneath the basement membrane was similar in RDA and LSA and did not change significantly after FP. This study shows that recent compared to long-standing mild asthma is associated with a similar degree of airway inflammation and subepithelial fibrosis, and a similar improvement in airway hyperresponsiveness after 8 wk on high-dose ICS. It also indicates that once asthma becomes symptomatic, airway responsiveness cannot normalize in most subjects over such a time period, even with a high dose of ICS.

Administration, Inhalation↗

PubMed1998

Changes in lung volumes and poor perception of bronchoconstriction-induced respiratory symptoms.

BACKGROUND: Changes in lung volumes may contribute to the perception of bronchoconstriction-induced breathlessness. AIM: To verify whether histamine-induced increases in lung volumes are more marked in asthmatic subjects with normal compared with low symptom perception scores and whether changes in lung volumes are detected similarly in both groups of subjects. METHODS: A group of 16 asthmatic subjects with low (< or =1) breathlessness score (scale: 0 to 10) at 20% fall in FEV1 (PS20B) on at least one of 2 histamine inhalation tests (HIT) performed on separate days (hypoperceivers) were studied. They were compared with a group of 12 asthmatic patients with a PS20B >1 on the 2 tests (normoperceivers). Lung volumes were measured before and after the second HIT and changes correlated with PS20B and PS20 for the sensation of chest tightness PS20CT) and with the slopes of these perception scores/% fall in FEV1 (PS B or CT/deltaFEV1). RESULTS: Hypoperceivers had a mean (+/-sem) PS20B of 1.03+/-0.20 on HIT1 and 0.66+/-0.12 on HIT2 (P>.05) and normoperceivers 2.59+/-0.14 on HIT1 and 2.38+/-0.18 on HIT2 (P>.05). Subjects' age, gender, duration of asthma, medication needs, and baseline and post-HIT pulmonary function (FEV1, FVC, FRC) were not significantly different between the two groups. Contrary to PS20B (P<.0001), PS20 for chest tightness (PS20CT) was similar in the two groups (HIT 1/2; hypoperceivers: 1.41/1.07, normoperceivers: 1.57/1.99, both P>.05). Perception of bronchoconstriction-induced breathlessness was not correlated with the degree of reduction in FVC at 20% fall in FEV1. In normoperceivers, (PS B/deltaFEV1) was significantly correlated with the postchallenge increase in FRC (rs = 0.63, P=.036) although there was no significant correlation in hypoperceivers (rs = -0.041, P>.05). CONCLUSION: Changes in lung volumes were similar in hypoperceivers and hyperperceivers of bronchoconstriction. Perception of breathlessness, however, was positively correlated with changes in lung volumes in normoperceivers but not in hypoperceivers suggesting that normoperceivers have an ability to detect these changes, presumably through proprioception, ability that is lacking or lost in hypoperceivers. More subjects should be studied to confirm this finding.

Adult↗

PubMed1998

Influence of beclomethasone and salmeterol on the perception of methacholine-induced bronchoconstriction.

BACKGROUND: Patient evaluation of asthma severity and medication needs is mostly based on respiratory symptoms and may be influenced by changes in perception of bronchoconstriction-induced sensations. However, the influence of asthma medication on the ability to perceive symptoms is still to be documented. This study evaluated the effects of short-term and regular use of salmeterol on the perception of methacholine-induced bronchoconstriction (MIB) in subjects with mild asthma, using inhaled salbutamol on an "as required" basis (n=15), and in subjects with moderate asthma, using daily inhaled beclomethasone (mean daily dose, 640 microg; n=15) in addition to salbutamol to control their asthma. METHODS: Methacholine challenges (MC) were performed at entry into the study, and then before, 1, and 12 h following inhalation of 50 microg of salmeterol or a placebo, after a 15-day baseline period; and after 4 weeks of twice daily use of those treatments. The measurements were then repeated with the alternate treatment after a 15-day washout period. Finally, a last MC was performed after another 15-day washout period. For each MC, the perception score of bronchoconstriction-associated breathlessness at 20% fall in FEV1 (PS20) was evaluated on a modified Borg scale from 0 to 10. RESULTS: Subjects using regular beclomethasone had a higher baseline PS20 than those using only salbutamol (means: 3.06 0.06 and 2.01+/-0.07, p=0.0001). Short- and long-term use of salmeterol did not change significantly the PS20 compared with placebo (p>0.05) in either group (with or without corticosteroid). Although there were some intraindividual variations, mean PS20 did not vary significantly throughout the study. CONCLUSION: These observations show that the perception of bronchoconstriction-associated breathlessness is not influenced by regular use of salmeterol. Patients using inhaled corticosteroids show a greater perception of MIB.

Administration, Inhalation↗

PubMed1997

Inhibitory effects of BAY x 7195, a CYS leukotriene 1 receptor antagonist, on allergen-induced asthmatic responses.

BACKGROUND: Leukotriene antagonists may inhibit bronchoconstrictive responses to a variety of stimuli. OBJECTIVE: To evaluate the efficacy and safety of a new CYS LTI antagonist, BAY x 7195, given as a single oral dose of 500 mg, in prevention of allergen-induced asthmatic responses. METHODS: This is a randomized, double-blind crossover, placebo-controlled study in mildly asthmatic non-smoking subjects (n = 10), aged 20 to 32 years (mean 24.8). Following an initial baseline allergen challenge, the subjects came back for two other challenges separated by at least a 2-week period, during which placebo or BAY x 7195 was administered two hours before allergen inhalation. Allergen challenges were preceded and followed by a methacholine inhalation test (24 hours before and 30 hours after). RESULTS: For each subject, the same allergen and doses were used throughout the study. In the randomized (intent-to-treat) population (n = 10), after BAY x 7195, the allergen induced % fall in FEV1 was less than after placebo, with mean between-treatment differences of 31.8 +/- 18.0% during the early asthmatic response, P = .03, and of 54.4 +/- 23.2% during the late asthmatic response (P = .04). The allergen-induced increase in methacholine responsiveness was reduced after BAY x 7195, with a change of -0.45 doubling concentrations of methacholine as compared with -1.77 after placebo; however, the change did not achieve statistical significance, P = .08. CONCLUSION: BAY x 7195 shows suppressive effects on allergen-induced responses, suggesting that it may be useful in the treatment of asthma.

Adult↗

PubMed1997

Characteristics of bronchial asthma with incomplete reversibility of airflow obstruction.

BACKGROUND: Incomplete reversibility of airflow obstruction (IRAO) can be observed in some asthmatic patients without significant smoking history nor evidence of other respiratory condition. The characteristics of this group remain however to be defined. METHODS: We compared 18 asthmatic patients with persistent airflow obstruction, defined as an FEV1 < or = 75% predicted despite optimal corticosteroid treatment, to others with complete reversibility of airflow obstruction, paired for age and gender (CRAO, FEV1 > 80% of predicted). RESULTS: Mean duration of asthma was 31.6 years for IRAO patients and 17.7 for the CRAO group and mean baseline FEV1 was 48.6 +/- 2.6% and 89.3 +/- 3.4%, respectively. Patients with IRAO had more severe airflow obstruction and hyperinflation than those with CRAO, while lung compliance and CO diffusion were similar. Overall healthcare use was similar in the two groups, but those with IRAO had a greater global asthma-related discomfort, increased diurnal variation of airflow obstruction and used higher doses of inhaled corticosteroids than those with CRAO. Patients with IRAO had slightly increased airway wall thickness on high resolution chest tomography compared with CRAO. Baseline FEV1 however, was not correlated with the measured airway wall thickness. CONCLUSION: We found that asthmatic patients with IRAO have a more severe asthma and asthma of longer duration than asthmatic subjects with CRAO. Our data suggest that in asthma, IRAO may result from long-standing airway inflammation and associated structural changes, although this remains to be further documented.

Administration, Inhalation↗

PubMed1997

Bronchial subepithelial fibrosis correlates with airway responsiveness to methacholine.

OBJECTIVES: To evaluate the relationships between airway subepithelial collagen deposition and epithelial desquamation with airflow obstruction and hyperresponsiveness in different types of asthma and other respiratory conditions such as chronic cough and allergic rhinitis. DESIGN AND PARTICIPANTS: We compared the histopathologic features observed on bronchial biopsy specimens obtained from 80 subjects: 38 with different types of asthma, 19 with chronic cough, 13 with allergic rhinitis, and 10 normal control subjects. Each subject had a questionnaire on respiratory symptoms and medication needs, measurements of expiratory flows and methacholine responsiveness, allergy skin prick tests, and a bronchoscopy with bronchial biopsies. None of the subjects studied used bronchial anti-inflammatory agents. RESULTS: Different degrees of bronchial subepithelial fibrosis were present in asthmatic subjects, the most intense being observed in occupational asthma; a subepithelial deposition of collagen was also found in subjects with allergic rhinitis, although it was less intense than in asthma and irregularly distributed under the basement membrane. On global analysis, we found a significant correlation between individual provocative concentration of methacholine inducing a 20% fall in FEV1 (PC20) and subepithelial fibrosis intensity (rs=-0.70, p<0.001). The degree of epithelial desquamation was correlated with that of subepithelial fibrosis (rs=0.36, p=0.02) in subjects with normal airway responsiveness, but it was not correlated with the PC20 (rs=0.10, p>0.05). Neither the degree of subepithelial fibrosis nor epithelial desquamation was correlated with the FEV1. CONCLUSION: These results suggest that structural airway changes such as subepithelial collagen deposition may be significant determinants or markers of a process that results in airway hyperresponsiveness.

Adult↗

PubMed1997

Comparative degree and type of sensitization to common indoor and outdoor allergens in subjects with allergic rhinitis and/or asthma.

BACKGROUND AND OBJECTIVES: The determinants of variability in the clinical expression of atopy are still to be documented. The goals of this study were to determine, in subjects with a clinical diagnosis of symptomatic asthma or rhinitis, what is the possible contribution of different types of indoor and outdoor allergens to the development of their disease, by looking at the prevalence and degree of sensitization to these allergens according to age and gender. SUBJECTS AND METHODS: We analysed allergy skin prick tests to common airborne indoor and outdoor allergens in 3371 consecutive patients, grouped according to diagnosis of allergic asthma, rhinitis, or both. For each of these three groups, we calculated the prevalence of sensitization to indoor/outdoor allergens, the atopic index (AI), the number of positive responses to allergy skin prick test and the mean wheal diameter (MWD) of these responses. RESULTS: The prevalence of atopy and the values of AI and MWD peaked in subjects aged 16 to 25 years, declining afterwards; in subjects > or = 18 years old, atopic indices were slightly higher in men than in women. In atopic subjects, the prevalence of sensitization was, in decreasing order, housedust (84.2%), cat hair-epithelium (76.5%), dog hair-dander (63.0%), house dust mite (54.2%), grasses (51.9%), trees (47.2%) and ragweed pollens (44.9%) and finally, moulds (25.4%). Among subjects sensitized only to outdoor allergens (n = 195). 73.8% had a rhinitis, 11.8% had asthma and 14.4% had both diagnoses; for those sensitized only to indoor allergens (n = 710), these values were respectively 48.6, 24.5 and 26.9%, and for those sensitized to both indoor and outdoor allergens (n = 1793), the comparable values were 55.5, 14.6 and 29.9%. CONCLUSION: These data show that in our population of subjects with respiratory allergic symptoms, indoor allergen sensitization is strongly associated with asthma, while exclusive sensitization to pollens is associated primarily with rhinitis. Sensitization was more prevalent for indoor allergens than for outdoor allergens in all groups determined according to diagnosis or age. Indices of atopy were higher in men in the group > or = 18 years old. Prevalence and degree of sensitization were shown to peak in young adults, regardless of the allergen, and to diminish with age. This study stresses the role of indoor allergens in the development of asthma and shows the variability of allergic manifestations according to the type of sensitization.

Adolescent↗

PubMed1995

Increased maximal airway response to methacholine during seasonal allergic rhinitis in nonasthmatic subjects: relationships with airway wall thickness and inflammation.

This study was carried out to determine whether the increase in airway responsiveness induced by natural antigenic exposure in nonasthmatic subjects is associated with an increase in maximal bronchoconstrictor response (MBR), and if these changes could be due to an increase in airway wall thickness from allergen-induced increase in airway inflammation. In 11 nonasthmatic subjects with seasonal allergic rhinitis, a methacholine challenge was obtained monthly, during and out of pollen exposure. Each subject had a high-resolution chest tomography in and out of the pollen season, to determine the relative thickness of the right intermediary bronchus over its total diameter (T/D), as well as inflammatory cell counts, apparent basement membrane thickness as an indication of subepithelial fibrosis and epithelial desquamation in bronchial biopsy specimens. In season, the mean provocative concentration of methacholine producing a 20% decrease in forced expiratory volume in one second (PC20) decreased from 51.5 to 25.8 mg.mL-1, and the maximal post-methacholine fall in forced expiratory volume in one second (delta FEV1,max) or forced vital capacity (delta FVC) and the slope of the dose response curve (DRS) increased compared with out of season: delta FEV1,max 44 +/- 5 vs 25 +/- 5%; delta FVC 34 +/- 5 vs 16 +/- 4%; and slope of DRS 14.1 +/- 2.8 vs 6.9 +/- 1.3%/mg.mL-1. No significant change was observed in T/D ratio. The seasonal change in delta FVC was positively correlated with the delta FEV1,max (rs = 0.891) and the change in DRS (rs = 0.909), but not with the change in PC20, nor with changes in bronchial biopsy inflammatory features or T/D ratio.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1994

Persistence of airway obstruction and hyperresponsiveness in subjects with asthma remission.

This study was designed to determine if there is residual airflow obstruction and/or airway hyperresponsiveness in adults with symptomatic asthma remission, and if age at remission or its duration influence these parameters. We studied 30 subjects, (20 men, 10 women, 28 atopics, aged 18 to 61 years; mean, 32 years) with a history of asthma (mean duration, 2 to 33 years) but who reported no symptoms or medication requirement for > or 2 years. They were individually matched for age, sex, and atopy, to a control group of 30 subjects without history of asthma. Each subject had a respiratory questionnaire and measurements of expiratory flows, lung volumes, and bronchodilator response. Morning/evening peak expiratory flow rates (PEFRs) were recorded for a 2-week period and two methacholine inhalation tests were obtained on separate days. Initial FEV1 and FVC for ex-asthmatics (controls) were, respectively, 91.0 +/- 2.5 percent and 97.8 +/- 2.3 percent (104.1 +/- 1.9 and 104.0 +/- 1.8 percent) of predicted values. Twenty nine ex-asthmatics (15 controls) had occasional respiratory symptoms, not attributed to asthma. Most subjects with asthma remission had evidences of mild airflow obstruction, associated to a methacholine response either increased in 11 (PC20 methacholine, 0.18 to 5.6 mg/ml) or "borderline" in 10 others (PC20 between 8 and 20 mg/ml). Airway responsiveness was normal (PC20 > 20 mg/ml) in 8 ex-asthmatics and in 21 controls (PC20 was under 8 mg/ml and between 10 and 20 mg/ml in, respectively, 5 and 4 controls). Mean reversibility of FEV1 after 200 micrograms of albuterol was 5.7 (range, -1.1 to 14.1 percent) compared with 2.5 (-4.4 to 10.5) in controls. Mean and maximal diurnal variation of PEFR were, respectively, 4.6 +/- 0.4 percent and 12.3 +/- 1.3 percent (controls, 2.9 +/- 0.3 and 7.0 +/- 0.8 percent). There was a significant correlation between PC20 and age at the diagnosis of asthma or at the onset of remission. Airway responsiveness was significantly less when asthma or remission of asthma occurred at a younger age, although there was no difference for baseline FEV1 and no significant correlation between PC20 and duration of asthma or of remission. Perception of bronchoconstriction was similar in both controls and ex-asthmatics. In conclusion, most ex-asthmatics who considered to be in asthma remission showed a persistent increase in airway responsiveness with or without mild airflow obstruction, suggesting that symptom report may be insufficient to determine that asthma is in true remission.

Adolescent↗

PubMed1994

Perception scoring of induced bronchoconstriction as an index of awareness of asthma symptoms.

Perception of asthma symptoms shows a wide interindividual variability. Poor perception of airflow obstruction may lead to undertreatment of asthma. We reviewed the possibility of using a simple test to detect poor perceivers of bronchoconstriction as part of the investigation of asthmat. We studied 150 consecutive subjects referred for assessment of airway responsiveness. All had a histamine PC20 within the asthmatic range (< 16 mg/ml) and a fall in FEV1 of < 20 percent after saline inhalation. On histamine challenge, before each FEV1 measurement, perception of dyspnea was assessed on a modified Borg scale. A perception score of breathlessness at 20 percent fall in FEV1 (PS20) was obtained by interpolation of the two last points on the perception/fall in FEV1 curve. It was concluded that in a hyperreactive population, PS20 (1) showed a normal distribution pattern; (2) was similar in both genders; and (3) increased with age due to high postcontrol saline inhalation scores. Hypoperceivers or hyperperceivers were similar for age, sex, baseline FEV1, and PC20. The PS20 determination may be a useful additional parameter to obtain during provocation tests to assess perception of symptoms associated with bronchoconstriction. Its correlation with clinical outcome remains, however, to be determined.

Adolescent↗

PubMed1994

Comparative safety and efficacy of single or twice daily administration of inhaled beclomethasone in moderate asthma.

OBJECTIVES: In the treatment of stable mild to moderate asthma, twice-daily administration of inhaled steroids may allow adequate control of the asthma; however, comparisons of the efficacy of once- or twice-daily administration brought contradictory results. This study is a randomized, double-blind crossover trial, set to determine if inhaled beclomethasone dipropionate given once daily in the late afternoon or at bedtime can be as effective as a twice-daily regimen in the treatment of moderate asthma. DESIGN: Subjects were randomly assigned to 3 different dosing regimens of inhaled beclomethasone: (1) regimen A, a twice-daily dose of 500 micrograms in the morning and at bedtime; (2) regimen B, a single dose of 1,000 micrograms in the late afternoon; and (3) regimen C, a single dose of 1,000 micrograms at bedtime. PATIENTS AND PARTICIPANTS: Enrolled in the study were 42 subjects who required 500 micrograms of inhaled beclomethasone dipropionate twice daily to control symptoms of asthma and to minimize use of beta 2-adrenergic agonists, according to criteria suggested in a recent international consensus on asthma therapy. Prior to receiving therapy with inhaled steroids, all of these patients either had chronic symptoms of asthma that required administration of a short-acting beta 2-agonist at least twice per day, or had nocturnal asthma symptoms at least once per week. THERAPY: After a 2-week baseline evaluation, each subject was given the 3 treatment regimens in randomized order, each for a period of 4 weeks. Subjects were asked to record daily symptoms of asthma and peak expiratory flows in the morning and evening. At the end of each treatment period, spirometric data and airway responsiveness to methacholine were measured. MEASUREMENTS AND RESULTS: Thirty-seven subjects completed the study. No significant difference was found among the 3 treatment regimens for asthma symptoms, FEV1, the provocative concentration of methacholine causing a 20 percent decrease in the FEV1 (PC20) (geometric means, 1.41, 1.09, and 1.09 mg/ml), and mean morning and evening peak expiratory flow rates (PEFR). The plasma cortisol level and the adrenocorticotropic hormone (ACTH) response were not significantly different among treatments, nor were side effects, which were minimal. CONCLUSION: In moderate asthma controlled with a twice-daily dose of inhaled beclomethasone, a single total daily dose administered in the late afternoon or in the evening provides as good control of asthma for 2 months.

Administration, Inhalation↗