Distinct temporal patterns of immediate asthmatic reactions due to high- and low-molecular-weight agents.

BACKGROUND: Exposure to occupational agents can cause immediate asthmatic reactions. OBJECTIVE: It can be hypothesized that the pattern of immediate reactions is different for high (HMW)- and low-molecular-weight (LMW) agents. To test this, we studied the temporal features of reactions in workers who underwent specific inhalation challenges for possible occupational asthma. METHODS: We examined 467 immediate reactions due to HMW (n = 248, 53%) and LWW (n = 219, 47%) agents in regards to timing of the maximum reaction and recovery. RESULTS: The median duration of exposure to elicit significant immediate reactions was comparable for HMW and LMW agents (15 min). The median maximum fall in FEV (1) occurred after 20 min for LMW by comparison with 10 min for HMW agents (P < 0.001). The median timing of recovery of FEV (1) to 10% baseline was shorter for HMW (60 min) than for LMW (90 min) agents (P < 0.01), and significantly more subjects recovered to 10% baseline (89.5%) for HMW than for LMW agents (72.6%) (P < 0.001). Confounding variables such as age, atopy, baseline airway calibre and the maximum fall in FEV (1) at the time of the immediate reaction did not alter the significant effect of the nature of the agent per se. Immediate reactions were followed by a late asthmatic reaction more often in the case of LMW (37.3%) than HMW (26.2%) agents (P < 0.05). Significant changes in non-specific bronchial responsiveness were significantly (P = 0.02) more frequent after reactions to LMW (31.9%) than to HMW (21.4%) agents. We found similar trends by comparing reactions to flour (n = 113), the principal cause of reactions to HMW agents, and diisocyanates (n = 111), the principal LMW agent. CONCLUSIONS AND CLINICAL RELEVANCE: This study shows distinct patterns for immediate reactions due to occupational agents. These results can provide useful guidelines for performing specific inhalation challenges and improve the safety of the procedure.

Association of bronchial reactivity to occupational agents with methacholine reactivity, sputum cells and immunoglobulin E-mediated reactivity.

BACKGROUND: Bronchial responsiveness and IgE-mediated reactivity are associated with specific bronchial reactivity to allergens. OBJECTIVE: Our aim was to examine whether airway inflammation also plays a role. METHODS: Retrospective analysis of all subjects who underwent specific inhalation challenges in the investigation of occupational asthma (OA) since 2000. Responsiveness to methacholine (PC(20) ) and levels of eosinophils and neutrophils in induced sputum on the control day were associated with the presence of OA (positive-specific inhalation challenge). In a sample of subjects exposed to wheat flour, we also examined the role of specific IgE- mediated reactivity (skin reactivity, specific IgE). RESULTS: PC(20) level was significantly more often normal in subjects with OA (35 of 129, 27% instances) by comparison with non-OA (15 of 189, 8% instances), but the positive predictive value of responsiveness to methacholine for OA was low (35%). Coupling information on the level of eosinophils to responsiveness to methacholine increased positive predictive values for OA from 39% to 69% depending on the thresholds used. The best balance of positive (69%) and negative (60%) predictive values was obtained in the case of normal PC(20) and eosinophils ≥3%. In a multivariate analysis carried out in 34 subjects exposed to wheat flour, responsiveness to methacholine, sputum eosinophils, skin weal size and levels of specific IgE were all significantly associated with OA to wheat flour. CONCLUSION AND CLINICAL RELEVANCE: Information on the level of sputum eosinophils in addition to PC(20) provides a better association with OA vs. non-OA when PC(20) is normal. Levels of sputum eosinophils in addition to PC(20) and IgE-mediated reactivity increase the likelihood of OA due to wheat flour.

Factors influencing duration of exposure with symptoms and costs of occupational asthma.

The most important factor for the prognosis of occupational asthma is the length of exposure with symptoms prior to removal from exposure. We wanted to identify factors, including socioeconomic status, that can influence the delay in submitting a claim to a medicolegal agency after the onset of asthmatic symptoms, and to confirm that this delay is associated with worse respiratory prognosis and higher direct costs. This is a cross-sectional study of subjects who claimed compensation for occupational asthma at the Workers' Compensation Board of Quebec, Canada. Data were collected at re-evaluation ∼2.5 yrs after diagnosis. Information on the number of years with symptoms and removal from exposure was obtained from the medicolegal file. 60 subjects were included in the study. Being older, having a revenue of >30,000 Canadian dollars and having occupational asthma due to high molecular weight agents were all positively associated with the number of years of exposure with symptoms before removal from exposure. Subjects with persistent airway hyperresponsiveness at follow-up had a higher number of years with symptoms. Experiencing symptoms in the workplace for <1 yr generated lower direct costs. These findings might help in surveillance programmes that could be preferentially targeted for these subgroups of workers.

Matrix metalloproteinases, IL-8 and glutathione in the prognosis of workers exposed to chlorine.

BACKGROUND: Workers exposed to chlorine may be at risk of deterioration in FEV1. METHODS: A prospective study of 72 workers examined over a 5.8 +/- 1.9 year period. A sample of induced sputum for cells and mediators was obtained in 69 subjects at baseline (Vb) and in 36 both at Vb and at follow-up (Vf). RESULTS: Sixty-four workers (89%) experienced at least one accidental inhalation of chlorine in the interval. The mean decrease in FEV1 was 30 ml/year and thus was within normal limits. Among the analysed remodelling markers, the level of the MMP-9-TIMP-1 complex, but not of free MMP-9 and TIMP-1, significantly diminished from Vb to Vf. We found significant correlations between neutrophils, IL-8, MMP-9 and MMP9-TIMP-1 complex at Vb and Vf. While levels of total glutathione, IL-8, MMP9, TIMP-1 and MMP9-TIMP-1 complex were highly correlated with each other at Vb, this was inconstant at Vf. Levels of MMP9-TIMP1 complex and of TIMP1 at Vf were significantly lower in workers reporting chlorine puffs with mild acute respiratory symptoms between visits compared to those who had no, or asymptomatic inhalations (P = 0.03 and 0.02, respectively). The fall in FEV1 from Vb to Vf was significantly correlated with levels of glutathione at Vb. Cough between visits was associated with a decrease in FEV1 (P = 0.06). CONCLUSION: Although no accelerated loss in FEV1 was documented in these workers exposed to chlorine, subjects with a greater fall in FEV1 were more likely to report cough and have higher levels of total glutathione at Vb.

Which tools best predict the incidence of work-related sensitisation and symptoms.

BACKGROUND/AIM: This study used information from the questionnaire alone or in conjunction with clinical tests, such as skin-prick testing (SPT) and bronchial responsiveness (BR) testing at entry, to develop models for estimating the probability of the occurrence of specific IgE-sensitisation to and respiratory symptoms in contact with laboratory animal (LA) allergens after 32 months' training in an animal health technology programme. METHODS: Four multivariable logistic regression models were developed for each endpoint, consisting of: (1) questionnaire; (2) questionnaire and SPT; (3) questionnaire and BR testing; and (4) questionnaire, SPT and BR testing. The prognostic models were derived from a cohort of Canadian animal health technology apprentices. The models' internal validity and diagnostic accuracy were evaluated and compared. RESULTS: Symptoms indicative of asthma and allergic symptoms at baseline composed the final questionnaire model for the occurrence of occupational sensitisation and symptoms. Both questionnaire models showed a good discrimination (area under the receiver operating characteristics curve were 0.73 and 0.78, respectively) and calibration (Hosmer-Lemeshow test p value >0.10). Addition of SPT and/or BR testing increased the specificity of the questionnaire model for LA sensitisation, but not for symptoms at work. To facilitate their application in practice, the final questionnaire models were converted to easy-to-use scoring system. CONCLUSIONS: Questionnaire is an easy tool that can give accurate prediction of the incidence of occupational sensitisation and symptoms.

Workplace-specific challenges as a contribution to the diagnosis of occupational asthma.

The diagnosis of occupational asthma can be made by exposing workers to the relevant agent either in a hospital laboratory through specific inhalation challenges (SICs) or in the workplace. As suggested by several authors, workers with negative laboratory SIC can be monitored at the workplace under supervision. The present study aims to assess the frequency of, and identify factors associated with, a positive workplace reaction in workers with negative SIC in the laboratory. The results of workplace challenges were examined in 99 workers who underwent negative SIC between 1994 and 2004. A positive reaction either in the SIC or in the workplace was defined as a sustained fall in forced expiratory volume in one second of > or =20%. In total, 22 (22.2%) workers showed positive responses at the workplace. These subjects more often had increased baseline methacholine responsiveness (90.5 versus 67.6%). They also underwent more days of SIC testing (4.9 versus 3.3 days) and were exposed more often to two or more agents (56 versus 28.4%) and for a longer period of time (363.3 versus 220.4 min) in the laboratory. The present study illustrates the usefulness of workplace monitoring of airway function in the investigation of occupational asthma and identifies factors that are more often associated with a positive reaction.

Structural changes and airway remodelling in occupational asthma at a mean interval of 14 years after cessation of exposure.

BACKGROUND: Occupational asthma (OA) may cause alterations of airways with inflammation and remodelling after cessation of exposure. Although the long-term clinical, functional and induced sputum sequelae have been examined in workers removed from exposure, the long-term pathological outcomes are unknown. OBJECTIVE: We aimed to investigate whether airway inflammation and remodelling were present in bronchial biopsies of subjects with prior OA but without evidence of persisting asthma at a mean interval of 14 years after cessation of exposure. METHODS: Ten clinically and functionally asymptomatic subjects with a prior diagnosis of OA were recruited and underwent bronchoscopy, bronchoalveolar lavage and bronchial biopsy. Comparisons were made with biopsies from normal control subjects. Epithelial detachment, epithelial metaplasia, mucous gland and airway smooth muscle (ASM) areas as well as the distance between the epithelium and ASM were measured by image analysis. The amount of collagen present was assessed by van Gieson staining. The numbers of TGF-beta1- and eosinophil cationic protein (ECP)-positive cells were evaluated by specific immunostaining. RESULTS: Statistically significant increases were found in the numbers of TGF-beta1- and ECP-positive cells and in the amount of subepithelial fibrosis present in the biopsies of subjects with prior OA compared with control biopsies. The distance between the epithelium and ASM was significantly reduced in the OA group. Increases in epithelial metaplasia, ASM mass, mucous gland numbers, collagen deposition and eosinophilia in the OA group were not statistically significant. There was no evidence of ongoing inflammation in the group with prior OA as assessed by the number of T lymphocytes present. CONCLUSION: Some aspects of airway inflammation and remodelling persist in subjects with prior OA long after cessation of exposure even in the absence of clinical, sputum and functional abnormalities. These findings are relevant to the assessment of long-term sequelae in subjects with OA when reviewed after cessation of exposure.

The reversibility of airway obstruction to an inhaled beta 2-adrenergic agent is less satisfactory after methacholine testing in asthmatic subjects.

AIMS: The aim of this work was to compare the response to an inhaled beta 2-adrenergic agent in two situations: (1) spontaneous airway obstruction in asthmatic subjects who had withheld treatment with the medication for more than 12 hs; and (2) after methacholine-induced airway obstruction once airway caliber had recovered to the premethacholine test value. SUBJECTS AND METHODS: Sixteen asthmatic subjects who showed a 20% or more improvement in FEV1 after inhaled beta 2-adrenergic agent (B2) (salbutamol, 200 micrograms) entered a double-blind crossover randomized trial in which the following tests were carried out: (1) FEV1 response after inhaling a placebo or active B2; (2) FEV1 response after inhaling a placebo or active B2 after a methacholine test that had induced a 20% or more reduction in FEV1, once FEV1 had recovered to the premethacholine value after inhaling salbutamol in an open fashion. RESULTS: As expected, the mean percent improvement in FEV1 in the spontaneous airway obstruction situation was 21.7 +/- 8.5% after inhaling the active B2 and 2.2 +/- 1.8% after placebo B2 (p < 0.001). Following recovery after methacholine challenge, the FEV1 was slightly superior (mean difference of 146 mL) to the premethacholine value before inhaling the active or placebo B2. In this situation, the percent improvement in FEV1 after inhaling the active B2 was only 7.5 +/- 4.4% and not significantly different from after inhaling placebo B2 (4.9 +/- 5.4%). Consequently, the end FEV1 value after inhaling active B2 was significantly higher in a situation of spontaneous airway obstruction than after methacholine-induced airway obstruction (mean difference = 110 mL; p = 0.02). CONCLUSION: After a methacholine test, the reversibility of an inhaled beta 2 agent is not significantly different from a placebo and is less satisfactory than in a situation of spontaneous airway obstruction. The mechanism for this needs to be explored but it is not secondary to persisting airway obstruction.

Duration of effect of loratadine and terfenadine administered once a day for one week on cutaneous and inhaled reactivity to histamine.

STUDY OBJECTIVE: The duration of action of several new non-sedative antihistamine preparations as assessed by skin and bronchial reactivity to histamine has still not been well established. The aim of the study was to evaluate the duration of effect of loratadine (10 mg) and terfenadine (120 mg) administered once a day for one week on cutaneous and inhaled reactivity to histamine by comparison with a placebo. SUBJECTS: Twenty-four adult asthmatic subjects were included in a parallel group study that compared the duration of effect of two antihistamines and a placebo on cutaneous and inhaled reactivity to histamine. STUDY DESIGN: Baseline cutaneous and inhaled reactivity (concentration causing a fall of 20 percent in FEV1 [PC20]) to histamine was obtained on three consecutive days. Loratadine (10 mg), terfenadine (120 mg) and a placebo loratadine were administered daily for 1 week to 3 groups of subjects. The PC20 was measured at the end of the medication period, 3 days later, and weekly until PC20 returned to baseline value (upper limit of 2 SD from the mean baseline value). RESULTS: The mean blocking duration on cutaneous reactivity for loratadine was 6.9 days and for terfenadine, 7.2 days. The mean duration of the blocking effect on PC20 histamine was 8.5 days for loratadine and 7.2 days for terfenadine. These figures were significantly longer than for the placebo. CONCLUSION: These data suggest that terfenadine and loratadine have a comparable blocking effect on reactivity to cutaneous and inhaled histamine. A daily dose taken for one week will result in a mean blocking effect of one week.

Comparison of peak expiratory flow rate and FEV1 in assessing bronchomotor tone after challenges with occupational sensitizers.

Bronchial responses to occupational sensitizers measured by peak expiratory flow rate (PEFR) and forced expiratory volume in 1 s (FEV1) during late reactions (between 90 minutes and 8 hours after exposure) were compared in two groups of 88 subjects who had undergone specific inhalation challenges in the laboratory. The first group had what was considered a positive reaction (a fall of at least 15 percent in FEV1) whereas the second group's reaction was interpreted as negative (fall in FEV1 less than 15 percent). Although the correlation in terms of percentage of change from baseline values was statistically significant, the correspondence was poor. PEFR proved far less sensitive than FEV1 in detecting a reaction. Whereas the mean maximum change in FEV1 overall was 27 percent, the mean maximum change in PEFR at the same time interval was only 16 percent. Moreover, individual correlations between the percentage of change in FEV1 and PEFR were satisfactory (r2 greater than 0.80) in only 32/88 subjects (36 percent). No subject who was considered to have a negative challenge according to FEV1 had a change in PEFR greater than 20 percent. We therefore conclude that changes in PEFR are far less sensitive than changes in FEV1 in detecting responses during late reactions to occupational sensitizers.

[Effect of an inhaled beta-2-adrenergic agent administered at the time of delayed bronchial reactions to occupational agents]. / Effet d'un agent bêta-2-adrénergique inhalé administré au moment des réactions bronchiques retardées après exposition à des agents professionnels.

We previously showed in a retrospective study that the acute response to an inhaled beta-2-adrenergic agent is marked in late asthmatic reactions (J Allergy Clin Immunology 1990;85:834). In a double-blind prospective study, we assessed the magnitude and duration of the effect of inhaled salbutamol (200 micrograms) compared to a placebo in 22 subjects who experienced late asthmatic reactions (sustained fall in FEV 1 > or = 20%) after specific inhalation challenges in the laboratory with various occupational agents (isocyanates in 9 subjects). Before salbutamol was administered, the % in FEV1 over the pre-challenge values did not differ between the placebo (31 +/- 8%, n = 12) and the active (28 +/- 6%, n = 10) groups. The % recovery in FEV1 over the pre-bronchodilator value was 9 +/- 11% in the placebo group and 28 +/- 11% in the active group (t = 4.0, p < 0.001). The % recovery in FEV1 assessed in comparison with pre-challenge values was up to 80 +/- 17% in the placebo group and up to 95 +/- 6% in the active group (t = 2.85, p < 0.01). The 10 subjects on active medication had FEV1 values > or = 80% of the pre-challenge value one hour after inhaling salbutamol. The pattern of diminution in the bronchodilator effect was similar in the eight subjects with occupational asthma on active medication who remained for more than one hour as compared to a control group of asthmatic subjects paired for the degree of baseline airway obstruction. These data show that late asthmatic reactions are satisfactorily reversed with inhaled bronchodilator and that the duration of the effect is as satisfactory for subjects with occupational asthma as it is for asthmatic subjects.

[Duration of bronchial protective effect of salmeterol in asthma induced by hyperventilation with dry cold air]. / Durée de l'effet bronchoprotecteur du salmétérol dans l'asthme induit par l'hyperventilation d'air froid sec.

The duration of the blocking effect of salmeterol (50 micrograms), albuterol (200 micrograms) and placebo was compared in a double-blind study carried out in 12 adult asthmatic subjects who underwent hyperventilation tests with cold dry air on 4 study days. On the first day, the hyperventilation test was carried out at various time intervals with spontaneous functional recovery between each test. The response was assessed by interpolating the dose of cold dry air causing a 20% fall in FEV1 (PD20). On the three other days, the active or placebo medications were administered. Spirometry was assessed 15 minutes and 1 hour later. The hyperventilation test was then performed and repeated at various time intervals after administering the drug. The mean duration of the blocking effect was 0.25 hour for placebo, 3.5 hours for albuterol, and of 15.9 hours for salmeterol. Eight of the 12 subjects still showed some blocking effect eight hours after salmeterol by comparison with only one subject after albuterol. The authors conclude that salmeterol has a significantly longer effect than albuterol on bronchoconstriction induced by hyperventilation.

[The Quebec system of indemnification for occupational asthma. Description, efficacy, and costs]. / Le système québécois d'indemnisation pour asthme professionnel. Description, efficacité et coûts.

This study describes the Quebec system of compensation for occupational asthma, assessing the functional and social outcome of claimants and estimating the efficiency and cost. Information was obtained on the clinical, functional and social outcome as well as the estimated costs for 134/211 subjects (participation rate of 64%), who received compensation between 1986 and 1988. At the time of assessment (2 years and more after the diagnosis), 93% of participants still demonstrated significant bronchial hyperresponsiveness and 84% required anti-asthma medication. None of the participants remained exposed to the offending agent: 67% were working for the same or another employer, 16% were retired, 8% were retraining for a new job and 8% were still unemployed. Quality of life was mildly affected, more so than for a control group of subjects. The mean interval between the time claims were addressed and the first medicolegal decision was 8.1 months. The mean total cost (including temporary and permanent disability indemnities, medical and technical costs) was $CAN 49,200 (minimum and maximum values of $2,100 and $330,900). We conclude that for subjects with occupational asthma in Quebec: 1) the mean interval for a medicolegal decision to be made is eight months: 2) a minority is still unemployed two to four years after being assessed; 3) the quality of life is more affected than in a control group; 4) the mean cost is close to $CAN 50,000.

Assessment of impairment/disability due to occupational asthma through a multidimensional approach.

Subjects with occupational asthma (OA) are often left with permanent sequelae after removal from exposure, and assessing their impairment/disability should utilise various tools. The aim of the present study was to examine whether: 1) assessment of inflammation in induced sputum is relevant to impairment; and 2) use of questionnaires on quality of life and psychological factors can be useful for the evaluation of disability. In total, 40 subjects were prospectively assessed for permanent impairment/disability due to OA 2 yrs after cessation of exposure. Impairment was assessed as follows: 1) need for asthma medication; 2) asthma severity; 3) airway calibre and responsiveness; and 4) degree of inflammation in induced sputum. Disability was assessed according to quality of life and psychological distress. There was a significant improvement in airway responsiveness and inflammation from diagnosis to the present assessment. Sputum eosinophils > or =2% and neutrophils >60% were present in eight (20%) and 12 (30%) out of all subjects, respectively, one or the other feature being the only abnormalities in 15% of subjects. Quality of life was moderately affected and there was a prevalence of depression and anxiety close to 50%. In the assessment of subjects with occupational asthma, information on airway inflammation and psychological impacts are relevant to the assessment of impairment/disability, although these findings need further investigation.

What are the questionnaire items most useful in identifying subjects with occupational asthma?

The present study assessed the usefulness of key items obtained from a clinical "open" questionnaire prospectively administered to 212 subjects, referred to four tertiary-care hospitals for predicting the diagnosis of occupational asthma (OA). Of these subjects, 72 (34%) were diagnosed as OA (53% with OA due to high-molecular-weight agents) according to results of specific inhalation challenges, and 90 (42%) as non-OA. Wheezing at work occurred in 88% of subjects with OA and was the most specific symptom (85%). Nasal and eye symptoms were commonly associated symptoms. Wheezing, nasal and ocular itching at work were positively, and loss of voice negatively associated with the presence of OA in the case of high-, but not low molecular-weight agents. A prediction model based on responses to nasal itching, daily symptoms over the week at work, nasal secretions, absence of loss of voice, wheezing, and sputum, correctly predicted 156 out of 212 (74%) subjects according to the presence or absence of OA by final diagnosis. In conclusion, key items, i.e. wheezing, nasal and ocular itching and loss of voice, are satisfactorily associated with the presence of occupational asthma in subjects exposed to high-molecular-weight agents. Therefore, these should be addressed with high priority by physicians. However, no questionnaire-derived item is helpful in subjects exposed to low-molecular-weight agents.

Exposure to a sensitizing occupational agent can cause a long-lasting increase in bronchial responsiveness to histamine in the absence of significant changes in airway caliber.

A 58-year-old subject with a history of occupational asthma to red-cedar sawdust underwent specific inhalation challenges with this product. Significant increases in airway responsiveness to histamine (tenfold fall in PC20 FEV1) were documented 7 hours after exposure for 5 minutes to red cedar while baseline spirometry remained unchanged. A dual asthmatic reaction was induced during the following days by exposing the subject to red-cedar sawdust for 30 minutes and plicatic acid for 7 minutes. After recovery of PC20, the subject was reexposed to plicatic acid for 15 and 30 seconds on 2 consecutive days. No significant changes in FEV1, forced vital capacity, and residual volume were demonstrated in the following 8 hours, although minimal changes in forced expiratory flow rate between 25% and 75% of FVC were observed. PC20 dropped significantly and required 2 weeks to recover. This example illustrates that bronchial hyperresponsiveness to histamine can precede the changes in airway caliber after an antigen challenge. It also demonstrates that such changes can persist for up to 2 weeks after the challenge, even when no significant changes in FEV1 are induced.

Significant changes in nonspecific bronchial responsiveness after isolated immediate bronchospecific reactions caused by isocyanates but not after a late reaction caused by plicatic acid.

Although late bronchospastic reactions after exposure to antigenic and sensitizing agents usually significantly alter bronchial responsiveness to histamine or methacholine, presumably by causing bronchial inflammation, isolated immediate bronchospastic reactions do not induce such changes. We studied three subjects who demonstrated different patterns of reaction. The first individual was diagnosed as having occupational asthma to red cedar. This was confirmed by specific inhalation challenges that resulted in late bronchospastic reaction. No significant changes in the provocative concentration of histamine causing a 20% fall in FEV1 (PC20) were found 1 day after this reaction. Two weeks later, serial assessments (five and six, respectively) of PC20 histamine were recorded on control days and up to 48 hours after exposure to plicatic acid, which caused a late bronchospastic reaction with a maximum fall of 37% in FEV1. No significant changes in PC20 were found; the maximum variations on control days were 0.36 to 0.74 mg/ml, and on active days, from 0.37 to 0.59 mg/ml. By contrast, two other subjects, who demonstrated isolated immediate reactions after exposure to diphenylmethane diisocyanate, had significant changes in PC20 histamine and methacholine, in one subject from 3.1 mg/ml to 0.6 mg/ml 8 hours after exposure, and in the other subject, from 61.0 to 7.4 mg/ml 7 hours after exposure, with recovery during the next few days. These examples demonstrate that the pattern of nonspecific bronchial responsiveness after immediate and late bronchospastic reactions can be different from what has previously been described. Immediate bronchospastic reactions may lead to bronchial hyperresponsiveness, whereas late asthmatic reactions do not always induce changes in bronchial responsiveness.(ABSTRACT TRUNCATED AT 250 WORDS)

Comparative effects of volume history on bronchoconstriction induced by hyperventilation and methacholine in asthmatic subjects.

The aim of this study was to find out if bronchodilatation following deep inspiration can be induced by the inhalation of a "natural" stimulus (hyperventilation of cold dry air), and if the effect is similar to that induced by methacholine. After baseline assessment of lung resistance (RL), 10 asthmatic subjects were asked to inhale cold dry air for 3 min. RL was monitored continuously for 3-4 min, at which time subjects were asked to take a fast deep inspiration. After recovery, the manoeuvre was repeated and RL was reassessed. The manoeuvre was then repeated a third time. After functional recovery, progressive doses of methacholine were inhaled until the increase in RL was comparable to that obtained after hyperventilation (56 +/- 16% and 65 +/- 24%, respectively, mean +/- SD, NS). The same deep inspiration manoeuvre was repeated three times with recovery as after hyperventilation of cold dry air. Maximum changes in RL were not significantly different after each of the three manoeuvres for either type of bronchoconstriction. The mean fall in RL was 14.2 +/- 9.9% after hyperventilation and 16.4 +/- 10.5% after methacholine. There was a satisfactory correlation (r = 0.80, p less than 0.01) between the bronchodilatation after deep inspiration for both types of stimuli. We conclude that the bronchodilator effect of deep inspiration is no different using either a pharmacological stimulus (methacholine) or a "natural" stimulus (hyperventilation of unconditioned air). These results show that assessing the response to hyperventilation with manoeuvres requiring deep inspiration, forced expiratory volume in one second (FEV1) may alter airway tone in a way similar to pharmacological stimuli.

Should we monitor peak expiratory flow rates or record symptoms with a simple diary in the management of asthma?

BACKGROUND: Various means of monitoring asthma severity have been proposed to reduce morbidity and mortality rates. We compared two means of assessing asthma flare-ups: monitoring peak expiratory flow rate (PEFR) and keeping a symptom diary. METHODS: This was a crossover randomized study. After a 2-week baseline period during which spirometry and PC20 methacholine were assessed, subjects were asked to record either PEFRs or to keep a symptom diary morning and evening for 6 months; a second baseline assessment separated the two periods. Subjects were asked to contact the study coordinator if the following occurred: (1) in the period of PEFR monitoring, daily fluctuations in PEFR were > 20% or the absolute value fell to < 80% of baseline or both occurred; (2) in the period of symptom diary monitoring there were nocturnal symptoms or a persistence of morning dyspnea after inhaled bronchodilator or a reduction in the duration of effect of the bronchodilator or it was impossible to go to work or school or all occurred. In that case they were asked to come to the hospital to confirm the flare-up through investigation for significant changes in FEV1 or PC20 or both. Forty subjects completed a 6-month symptom diary or PEFR recording period respectively, and 20 completed both. RESULTS: A total of 31 exacerbations were reported in 28 different subjects; three subjects had two flare-ups. Thirteen of 19 (69%) flare-ups were confirmed during the symptom diary period and 9 of 12 (75%) during PEFR monitoring. Nocturnal awakenings and morning falls in PEFR > or = 20% were the most frequent occurrences. CONCLUSIONS: We conclude that a simple symptom diary may be as useful as serial PEFR monitoring in documenting asthmatic flare-ups.

Is the clinical history a satisfactory means of diagnosing occupational asthma?

In some countries a diagnosis of occupational asthma for medicolegal purposes is made when a questionnaire is suggestive and the individual is exposed to a product known to be a sensitizer. The value of an open questionnaire administered by physicians with experience in occupational asthma is unknown, however. We prospectively assessed all subjects (162) referred to our clinic because their physicians thought their asthma might be work related. The medical questionnaire included questions about the nature of the symptoms (dyspnea, wheezing, cough, and chest tightness) and the timing (worse at work or after a shift at work or improved during weekends or holidays). An initial clinical assessment was set by the physician on a scale that ranged from highly probable to probable, uncertain, unlikely, or absent. Subjects then underwent objective assessment with specific inhalation challenges (n = 72), serial monitoring of peak expiratory flow rates for periods at work and away from work (n = 29), or both (n = 61), to confirm or rule out the diagnosis of occupational asthma. A total of 75 subjects (46%) were shown to have occupational asthma. Symptoms alone (type and timing) did not provide a satisfactory differentiation between those subjects with and those without occupational asthma. For example, 66 of 75 (88%) subjects with occupational asthma said that their symptoms improved during holidays, but 66 of 87 (76%) subjects without occupational asthma experienced a similar improvement.(ABSTRACT TRUNCATED AT 250 WORDS)