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J L Malo

Publications and source records attributed to J L Malo.

At least 19 recordsLinked to original sources
PubMed1992

[Non-allergen bronchial hyperexcitability and asthma: single and serial measurement].

Non-specific bronchial hyperresponsiveness (NSBH) is an essential characteristic of asthma. Its absence in a symptomatic individual virtually excludes asthma. Its presence is not synonymous with asthma although, in the absence of other obstructive or restrictive pulmonary conditions, it strongly suggests the diagnosis. The severity of NSBH is related to the degree of bronchial inflammation. Changes in NSBH are more frequent, although not constant, in late asthmatic reactions. The measurement of NSBH is useful in confirming or excluding a clinical diagnosis of asthma. It can also help in assessing the need for medication. Serial assessment of NSBH can be a useful tool in the follow-up of an asthmatic subject or in a subject investigated for occupational asthma although figures for sensitivity and specificity are low and preclude its routine use in these circumstances.

Asthma↗
PubMed1992

Occupational asthma caused by a prepolymer but not the monomer of toluene diisocyanate (TDI).

Isocyanates are the most common cause of occupational asthma. Isocyanate monomers and prepolymers are widely used in the manufacture of polyurethane compounds. However, prepolymers are generating increasing interest because of their lower volatility. No distinction has yet been made between asthmatic reactions caused by the monomers and the prepolymers of isocyanates, and asthmatic reactions caused by one type of isocyanate but not the other type have not been reported. We describe two wood-roof maintenance workers who developed asthma after being exposed to a varnish containing a prepolymer of toluene diisocyanate (TDI) with only small amounts of the monomer. Specific inhalation-challenge tests with the TDI monomer did not elicit significant airway obstruction, whereas exposure to the varnish and to the purified TDI prepolymer induced late asthmatic reactions. Specific antibodies against TDI monomer human serum albumin and TDI prepolymer human serum albumin conjugates could not be demonstrated. These observations demonstrate that isocyanate prepolymers can cause occupational asthma and that asthmatic reactions caused by isocyanate prepolymers, but not to the corresponding monomer, can occur in some exposed workers.

Adult↗
PubMed1992

Salmeterol, a new inhaled beta 2-adrenergic agonist, has a longer blocking effect than albuterol on hyperventilation-induced bronchoconstriction.

The duration of the blocking effect of salmeterol (50 micrograms), albuterol (200 micrograms), and a placebo were compared in a double-blind study in 12 adult subjects with asthma who underwent hyperventilation tests with cold dry air (-20 degrees C) on 4 study days. On the first day, the hyperventilation test was performed at various time intervals (baseline, 1, 4, 6, 8, 12, and 24 hours) with spontaneous functional recovery between each test to determine the within-day within-subject variability of the response. The response was assessed by interpolating the dose of cold dry air causing a 20% fall in FEV1. On the 3 remaining days, separated by an interval of at least 5 days, the active or placebo medication was administered after spontaneous recovery from the first hyperventilation test. Spirometry was assessed 15 minutes and 1 hour later. The hyperventilation test was then performed and repeated 4 hours after administration of the drug. The test was repeated 6, 8, 12, and 24 hours later to detect any significant blocking effect. The improvement in FEV1 15 minutes and 1 hour after the drug was administered was 19.8% and 20.4%, as compared to baseline for albuterol, and 16.3% and 16.8% for salmeterol (not significant). The mean duration of the blocking effect was 0.25 hour for the placebo, 3.5 hours for albuterol, and 15.9 hours for salmeterol (F = 24.5; p less than 0.001; Newman-Keul's test was significant for every contrast). Eight of the 12 subjects still demonstrated some blocking effect 8 hours after taking salmeterol; this was true for only one subject receiving albuterol.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1992

Natural history of occupational asthma: relevance of type of agent and other factors in the rate of development of symptoms in affected subjects.

It is unknown whether factors such as the nature of the agent, gender, age, atopy, smoking habits, continuous or noncontinuous exposure, and pattern of asthmatic reaction can influence the rate of development of symptoms in subjects with occupational asthma. We compared several clinical and functional parameters among three groups of subjects with occupational asthma caused by Western red cedar (group 1, n = 433), isocyanates (group 2, n = 107), and high molecular weight agents acting through an IgE-mediated mechanism (group 3, n = 121). Survival analysis showed that the three curves relating years of exposure before onset of symptoms to the proportion of subjects without symptoms were significantly different in two respects: (1) almost 40% of subjects in groups 1 and 2 as compared with 20% of subjects in group 3 became symptomatic within 1 year of exposure; (2) after 5 years of exposure, the rate of sensitization was slower for subjects in groups 2 and 3 as compared with those in group 1. Having a nonimmediate reaction at the time of specific inhalation challenges, being continuously exposed and being younger slightly increased the risk at each time point on the curve of developing symptoms in subjects with occupational asthma. These data suggest that the natural history for onset of occupational asthma is different depending on the sensitizing agent. Factors such as age, type of exposure, and pattern of reaction on exposure to the agent also modulate the rate of development of this condition.

Adult↗
PubMed1992

Closed-circuit methodology for inhalation challenge tests with isocyanates.

The diagnosis of isocyanate-induced occupational asthma can be made by exposing subjects to isocyanates in small challenge rooms. There are, however, several pitfalls inherent in this procedure. Isocyanate concentrations may not remain stable throughout the exposure and may exceed the recommended TLV ceiling of 20 ppb. This can induce irritant or unduly severe bronchial reactions. To overcome these problems, a closed-circuit apparatus for generating isocyanates in a gaseous form was developed; it was assessed in 20 subjects suspected of having isocyanate-induced asthma. Subjects were tested using both the small challenge room method and the new closed-circuit method in a randomized sequential way. Isocyanate concentrations were more stable with the closed-circuit apparatus than with the challenge room method (mean of individual variance of 6.3 and 61.8, respectively; p less than 0.001). The percentage of the total exposure time during which concentrations were above 20 ppb was reduced from 11.3 to 4.5% (p less than 0.001). The two methods yielded the same number of positive and negative responses, except for one subject who did not have a positive reaction when tested with the challenge room method. The pattern and magnitude of asthmatic reactions were similar for both methods. However, the duration of exposure was shorter with the challenge room method than with the closed-circuit methods (p = 0.04).

Administration, Inhalation↗
PubMed1992

Single-dose effect of astemizole on bronchoconstriction induced by histamine in asthmatic subjects.

STUDY OBJECTIVE: Astemizole, administered for seven days to asthmatic subjects, had an effect of bronchoconstriction induced by inhaled histamine for a mean period of 42 days. This study evaluates whether a single dose of astemizole would have the same effect. SUBJECTS: Sixteen adult asthmatic subjects took part in the study. DESIGN: They first underwent three inhalation tests and skin prick tests with histamine on three different days. On the last day, a methacholine inhalation test was also performed. They subsequently received either a placebo or an active preparation of astemizole. The histamine inhalation test was repeated one day, two days, one week, and/or ten days after administering the drug. RESULTS: Overall, no significant change in mean PC20 or in the mean diameter of the skin reaction to histamine was observed. However, three out of the eight subjects (38 percent) receiving active and none receiving placebo medication showed significant increases in PC20 histamine (p = 0.05). This effect lasted for one to two days. CONCLUSIONS: We conclude that a single dose of 10 mg/ml of astemizole can have a significant effect on bronchial but not cutaneous reactivity to histamine. This effect is of short duration (one to two days).

Adult↗
PubMed1992

Validation of an exposure system to particles for the diagnosis of occupational asthma.

STUDY OBJECTIVE: We previously described a closed-circuit system for exposure to particles in humans. This system has three components: a particle generator, an exposure chamber connected to an orofacial mask, and monitors. We describe results of challenges in 56 subjects who underwent challenges with the apparatus using occupational sensitizers in particles. SUBJECTS: Fifty-six consecutive subjects referred for the investigation of occupational asthma to occupational sensitizers in particles were included. The agents were the following: flour and grains (n = 19), cedar (n = 10), psyllium (n = 9), guar gum (n = 9), drugs (n = 3), persulfate (n = 2), and miscellaneous (n = 4). INTERVENTION: The duration of exposure was progressive and varied from one breath to a maximum of 180 min depending on the reaction. When no significant fall in FEV1 occurred after exposure with the aerosolization device, the standard approach of tipping particles from one tray to another was used. RESULTS: Twenty-nine subjects (52 percent) had a significant (greater than or equal to 20 percent) fall in FEV1 after exposure. This includes 18 subjects with isolated immediate reactions, four with dual asthmatic reactions, and two with atypical reactions. In 20/24 instances (83 percent), the percentage of fall in FEV1 did not exceed 30 percent, thus showing that dose-response curves can generally be obtained in a safe way. In all instances except one (26/27 cases), subsequent exposures using the traditional method did not result in significant falls in FEV1. CONCLUSION: This new procedure results in safe tests in terms of the percentage of changes in FEV1 during the immediate reactions and very rare false-negative challenges.

Aerosols↗
PubMed1992

[Duration of bronchial protective effect of salmeterol in asthma induced by hyperventilation with dry cold air].

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.

Adrenergic beta-Agonists↗
PubMed1992

Sustained improvement in asthma with long-term use of formoterol fumarate.

Inhaled formoterol fumarate, a long acting beta 2 agonist, produces bronchodilatation that is sustained for approximately 12 hours. To determine whether such bronchodilator effects are maintained and asthma control sustained during chronic administration, we monitored airflow indices and clinical control in 112 asthmatic patients who self administered formoterol twice daily for periods ranging from 9 to 12 months. Subjects were recruited immediately following completion of a 3-month double-blind comparison of formoterol, 12 micrograms, bid versus salbutamol, 200 micrograms, qid. Assessments were conducted at baseline, 3, 6, and 9 months, where baseline represents the final visit of the 3-month comparative study. Patients were asked to complete diary cards and twice daily PEFR for a 2-week period before each assessment. Throughout the follow-up study, there was no indication of worsening of asthma control or deteriorating lung function. For the patients who continued to receive formoterol, the previous improvement in asthma control and lung function was maintained at the level reached in the 3-month study. There was an improvement in flow rates and asthma symptoms in the group switched from salbutamol to formoterol by the first clinic visit. This improvement in asthma control and lung function was maintained over the subsequent 6 months. Formoterol was well tolerated during the study period. We conclude that prolonged use of formoterol fumarate twice daily results in sustained improvement in symptoms and flow rates in asthma with no evidence of tachyphylaxis.

Adolescent↗
PubMed1992

Update on an exposure system for particles in the diagnosis of occupational asthma.

We have previously designed a system for exposure to particles and described the preliminary results in 20 subjects exposed to occupational sensitizers in powder form (Cloutier Y, et al. - Eur Respir J, 1989; 2: 769). Modifications have been made to the particles generator, exposure chamber and sampling ports. Furthermore, in order to improve the stability of concentrations in the exposure chamber and to make the system easy to operate by a technician, it has been completely automated using closed-loop feedback regulated by a computer program.

Aerosols↗
PubMed1992

Occupational asthma: validity of monitoring of peak expiratory flow rates and non-allergic bronchial responsiveness as compared to specific inhalation challenge.

The sensitivity and specificity of monitoring peak expiratory flow rates (PEFR) and bronchial responsiveness to the provocative concentration of histamine or methacholine (PC20) has been determined as compared to specific inhalation challenges in the diagnosis of occupational asthma. A prospective study of 61 subjects referred for occupational asthma to various agents was performed. PEFR was assessed every 2 h during a period away from work for at least 2 weeks. The period at work was 2 weeks, or less if there was increased symptomatology or marked changes in PEFR. At least one PC20 assessment was obtained at work and away from work. Graphs of PEFR and PC20 values were interpreted in blind fashion by three experienced readers. There was complete agreement among the three in 54 out of 61 instances (78%). Twenty five out of 61 subjects (41%) had positive specific inhalation challenges. The best index for comparing results of PEFR with specific inhalation challenges was the visual analysis of PEFR with sensitivity and specificity of 81% and 74%. All of the numerical indices were significantly less satisfactory. We conclude that visual analysis of PEFR is an interesting tool for investigating occupational asthma, although sensitivity and specificity values do not seem satisfactory enough to warrant using it alone.

Adult↗
PubMed1992

[Budesonide: efficacy and indications of low posology].

Although inflammation plays a crucial role in asthma, asthma is not equivalent to inflammation. On the one hand, the relationship between the degree of airway inflammation and the level of bronchial responsiveness to pharmacological agents is not well established. On the other hand, even if late asthmatic reactions has many inflammatory characteristics, the response to the inhalation of a beta-2 adrenergic agent is generally good, which suggests some muscular contraction as well in the reduction of airway caliber. The chronic use of antiinflammatory preparations improves the level of bronchial hyperresponsiveness but this effect is not constant, does not generally result in-normal values and may be short-lived after ending the administration of the drug. It is unknown as to whether the chronic use of these preparations: 1) will reduce the mortality and morbidity of asthma; 2) will be devoted of long-term side effects; 3) will be accompanied by a satisfactory compliance. A greater awareness of these potential problems should therefore be kept in mind before prescribing low-dose inhaled steroids.

Administration, Inhalation↗
PubMed1991

Reassessment of the temporal patterns of bronchial obstruction after exposure to occupational sensitizing agents.

Typical asthmatic reactions after exposure to common or occupational allergens have been classified as isolated immediate, early late, late, and dual (Pepys and Hutchcroft, 1975). Atypical reactions can also occur, but their temporal behavior and frequency are unknown. We analyzed 69 bronchospastic reactions after exposure to three types of occupational sensitizers in the laboratory: isocyanates, western red cedar, and IgE sensitizing agents. Graphs of the reactions were presented to three observers in a blind, randomized way. Reactions were defined as follows: (1) typical patterns, that is, isolated immediate, early late, late, and dual, as put forward by Pepys and Hutchcroft, and (2) atypical patterns including progressive (onset, during, or minutes after exposure, progressing to a maximum reaction 5 to 6 hours later) and square waved (similar to a dual reaction but with only partial recovery [less than 10%] between the immediate and late falls in FEV1). Some curves were also analyzed by polynomial regression. The three observers agreed in 59/69 cases (86%), and a consensus was reached after discussion for the remaining subjects. Fifteen of 63 (22%) reactions were atypical. IgE-mediated reactions and reactions to red cedar were, respectively, mainly of the immediate and late types. The distribution of reactions to isocyanates, however, was significantly different (chi-square, 6.1; p = 0.01), the "progressive" pattern occurring in 7/23 instances (30%). There was a satisfactory concordance between visual assessment and polynomial fit analysis in distinguishing dual from square-waved reactions. We conclude that isocyanates frequently cause atypical progressive bronchospastic reactions that are rarely observed after exposure to IgE agents and western red cedar.

Adult↗
PubMed1991

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)

Adult↗
PubMed1991

A three-month comparison of twice daily inhaled formoterol versus four times daily inhaled albuterol in the management of stable asthma.

We compared the efficacy of inhaled formoterol, a long-acting beta 2-agonist, with inhaled albuterol in 145 stable adult asthmatics in a 12-wk multicenter trial. Patients were allocated in randomized double-blind fashion to maintenance therapy with either formoterol 12 micrograms twice a day or albuterol 200 micrograms four times a day in addition to their other asthma medications. Patients were allowed to use "rescue" 100-micrograms albuterol puffs on an as-needed basis. Mean baseline FEV, in the morning before bronchodilator was 2.14 +/- 0.76 L and 1.98 +/- 0.71 L for the formoterol and albuterol groups, respectively, these values being used as baseline covariates in subsequent analysis of predrug and postdrug FEV1. Measured at each clinic visit, morning predrug FEV1 rose significantly with formoterol treatment and was significantly greater at all visits than in the albuterol group, the greatest difference being in Week 8 (2.40 +/- 0.77 versus 1.92 +/- 0.66 L, p less than 0.001). Morning FEV1 30 min postdrug was significantly higher in the formoterol group at Weeks 2 and 8, the trend not reaching statistical significance at other times. Diurnal variation in prebronchodilator peak flow rates was significantly reduced in the formoterol group throughout the trial (17 versus 42 L/min at Week 12, p less than 0.0001). The number of asthma episodes per week was significantly less in the formoterol group during Weeks 4, 8, and 12 as were the number of sleep disruptions during Weeks 2, 4, 6, 8, and 12. Significantly more rescue albuterol was required in the albuterol group by Week 2 and throughout the remainder of the study.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Inhalation↗
PubMed1991

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.

Adult↗
PubMed1990

Late asthmatic reactions to occupational sensitizing agents: frequency of changes in nonspecific bronchial responsiveness and of response to inhaled beta 2-adrenergic agent.

Late asthmatic reactions have been demonstrated, generally, to increase bronchial responsiveness and are believed to respond poorly to inhaled bronchodilator. To assess the frequency of changes in bronchial responsiveness, we reviewed the records of 101 subjects with late asthmatic reactions and of 63 subjects with isolated immediate reactions after specific inhalation challenges to various occupational agents. These subjects had undergone nonspecific inhalation challenges to histamine or methacholine on a control day and after the late reaction when FEV1 had returned to +/- 10% baseline. We also reviewed 99 cases of subjects with late reactions who were administered an inhaled beta 2-agent (albuterol, 200 micrograms) during the late reaction. Fifty-seven/101 (56%) subjects with late reactions and 24/63 (38%) subjects with isolated immediate reactions demonstrated a twofold or greater change in provocative concentration of histamine or methacholine causing a 20% change in FEV1 (PC20) from baseline (p = 0.02; odds for the presence of significant changes in PC20 in subjects with late reactions, 56%; odds for the absence of significant changes in PC20 in subjects with immediate reactions, 62%). Changes in FEV1 greater than 20% after administering albuterol at the time of the late reactions occurred in 78% of the subjects tested; in 66%, FEV1 returned to greater than 90% baseline. This retrospective study demonstrates that changes in bronchial responsiveness after late reactions are not constant and do not appear to distinguish satisfactorily late from immediate reactions. Furthermore, late reactions respond well to beta 2-agonist.(ABSTRACT TRUNCATED AT 250 WORDS)

Albuterol↗