Respiratory bronchiolitis associated with interstitial lung disease.

Respiratory bronchiolitis associated with interstitial lung disease (RB-ILD), first described by Niewoehner et al in an autopsy study of cigarette smokers who died from non pulmonary causes in 1974, is a rare entity that should be distinguished from the other interstitial lung diseases and in particular from desquamative interstitial pneumonia, although the two conditions share a similar histopathological pattern. RB-ILD is clearly connected with tobacco smoking and has been inserted in the "smoking related interstitial lung diseases" together with DIP and Cell histiocytosis of Langerhans; it may also be associated with occupational exposure to machine fumes. The following is a case report of a patient with both smoking and occupational exposure.

Massive unilateral hydrothorax as the only clinical manifestation of ovarian hyperstimulation syndrome.

We describe the case of a 36 old woman with a right massive hydrothorax resulting from Controlled Ovarian Hyperstimulation (COH) for infertility. This complication is defined as Ovarian Hyperstimulation Syndrome (OHSS) which usually includes abdominal pain, nausea and ascites, rarely involving the respiratory apparatus. The usual determining factors of OHSS are the presence of high serum estradiol levels and pregnancy. In the case that we describe the serum estradiol levels during COH were monitored and were slightly higher than the COH alarm threshold and the patient was not pregnant.

A three-drug regimen (gemcitabine, ifosfamide and cisplatin) for advanced non-small-cell lung cancer.

We have carried out a pilot study on 25 non-small cell lung cancer patients, administering the combination of gemcitabine at the dose of 1000 mg/m2 on days 1 and 8, ifosfamide 1500 mg/m2 on days 1 and 2 (plus mesna as uroprotector) and cisplatin 40 mg/m2 on days 1 and 2, every 21 days. Granulocyte Colony Stimulating Factor was employed in all cases from day 10 to day 18 at the dose of 300 microg daily. An objective response was observed in 11 cases (44%). The regimen was active, but toxicity was remarkable with some cases of severe myelosuppression and mucositis.

Perception of methacholine-induced airway obstruction in asthmatics.

The main objective of this study was to examine the perception of the first symptom during methacholine bronchoconstriction as soon as it occurred, and in the second instance to quantify the intensity of the breathlessness by means of the Borg Scale performed at the end of challenge so to not determine any difficulties for identification of the first symptom. A methacholine challenge test was carried out in 139 symptom-free asthmatics with a normal pulmonary function. When the first symptom was reported by the subject, the forced expiratory volume in one second (FEV1) was measured immediately. FEV1 was expressed as a percentage of the best personal value (FEV1%BPV). The intensity of the breathlessness was rated using a modified Borg Scale at the end of the challenge test so as not to confuse the patient. Seven subjects felt nothing during challenge. The first symptoms varied: constriction behind the breastbone (49%), inspiratory shortness (16.5%), coughing (10%), wheezing, throat constriction, general chest tightness, pain behind the sternum, and a sensation of rheum behind the sternum. FEV1%BPV at the first symptom was 80.5 +/- 10 (range 41-99). No symptom was perceived by 42% of the subjects within the 80-100 range of FEV1%BPV. FEV1%BPV at the first symptom was related to the log of the provocative dose causing a 20% fall in FEV1 (r = 0.2, p < 0.05). An inverse correlation between Borg Score and final FEV1%BPV (r = -0.25, p < 0.01) was found at the end of challenge. A subgroup of 39 subjects with similar final FEV1%BPV values (68-72) showed a correlation between the Borg Score at end of challenge and FEV1%BPV at the first symptom (r = 0.59, p < 0.001). The first symptom of the methacholine-induced bronchoconstriction varies in asthmatics and may be atypical, the bronchoconstriction level at which it is felt also varies among individuals, highly methacholine-responsive subjects perceive the bronchoconstriction later, while late perceivers of the first symptom show less intense breathlessness at the end of challenge. The measurement of the patient's ability to perceive asthmatic symptoms during the methacholine challenge test could be used to single out poor perceivers.

Sequential high dose-density chemotherapy with two active regimens for advanced small cell lung cancer.

16 patients with advanced small cell lung cancer were treated with a combination of cyclophosphamide (1000 mg/m2 day 1), epidoxorubicin (60 mg/m2 day 1) and vincristine (1.4 mg/m2 day 1) every 14 days for six cycles followed by a combination of cisplatin (40 mg/m2 days 1 & 2) and etoposide (100 mg/m2 days 1-3) every 14 days for four cycles. Shortening of intervals was obtained with the prophylactic employment of granulocyte colony-stimulating factor (filgrastim, 300 mcg subcutaneously from day 5 to dsy 10). In 11 patients ratio between actually delivered dose intensity and planned dose intensity of > 80% was obtained. Toxicity was acceptable and no life-threatening toxicities were observed. An objective response (partial or complete) was observed in 11 patients. The new regimen, incorporating the concepts of dose-intensification and sequential administration of regimens, is feasible and may be considered for further studies.

Salmeterol versus slow-release theophylline in patients with reversible obstructive pulmonary disease.

A 1-yr multicentre two-tailed randomized open study was conducted in 15 centres in Italy, with the aim of comparing the clinical efficacy (over 3 months) and tolerability (over 1 yr) of salmeterol with those of oral theophylline in patients with reversible chronic obstructive pulmonary disease (COPD). Patients with reversible COPD (forced expiratory volume in one second (FEV1) 50-80%, FEV1 after bronchodilator > 12%, n = 138) were randomized to receive salmeterol powder (50 micrograms b.i.d. with Diskhaler, n = 66) or individually dose-titrated slow-release oral theophylline capsules so as to obtain a serum concentration of theophylline ranging 10-20 micrograms.mL-1 (n = 72). During the 2-week run-in period, nonadmitted medications were discontinued and patients had to present with respiratory symptoms on at least four of the last seven days. Following randomization, patients were required to monitor daytime and night-time symptoms, additional use of as-required salbutamol, and morning and evening peak expiratory flow (PEF) for 3 months. Spirometric measurements and assessment of the quality of life were performed every 3 months for 1 yr. Salmeterol was proven to be statistically more effective than theophylline in: 1) increasing the maximum value of morning PEF; 2) increasing the percentages of days and nights without symptoms; 3) reducing the need for additional salbutamol during daytime and night-time; and 4) increasing quality of life in terms of physical and social activities, mental health and psychophysical energy, assessed 3 months after the beginning of treatment. Salmeterol was no more effective than theophylline in increasing: 1) forced vital capacity and FEV1 at the various measurements; 2) maximum evening PEF value; and 3) quality of life after the first 3 months of treatment. Neither treatment induced significant side-effects over the 1-yr treatment. This study confirms that inhaled salmeterol is more effective than oral theophylline in long term treatment of reversible obstructive pulmonary disease.

A phase II study of a three-drug combination (cisplatin, ifosfamide and vinorelbine) plus granulocyte-colony stimulating factor in advanced non small cell lung cancer.

Twenty-nine patients with advanced non-small-cell lung cancer (NSCLC) were treated with a combination of cisplatin 20 mg/m2 days 1-3, ifosfamide 1500 mg/m2 days 1-2 (plus mesna as uroprotector) and vinorelbine 25 mg/m2 days 1 and 5; filgrastim was given at the dose of 300 microg subcutaneously from day 8 to day 15. A response rate of 28% was observed. The activity of this combination in an outpatient setting, with acceptable toxicity, has been demonstrated.

Effect of a single dose of salmeterol on the increase in airway eosinophils induced by allergen challenge in asthmatic subjects.

BACKGROUND: The long acting beta2 agonist salmeterol is very effective in preventing asthmatic responses to specific stimuli, and this effect could theoretically be due to some anti-inflammatory property in addition to bronchodilator property. METHODS: The protective effect of a single dose of salmeterol (50 microg) on allergen induced early and late responses and on the associated airway inflammation was investigated in a double blind, placebo controlled, crossover study in 11 atopic asthmatic subjects. Eosinophil percentages and concentrations of eosinophil cationic protein (ECP) in peripheral blood and in hypertonic saline induced sputum were measured 24 hours after allergen inhalation. RESULTS: Salmeterol effectively inhibited both early and late asthmatic responses in comparison with placebo. Salmeterol also inhibited the increase in the percentage of eosinophils in the sputum 24 hours after allergen inhalation (median (range) baseline 6% (1-36), after placebo 31% (5-75), after salmeterol 12% (1-63)). However, the increase in both sputum and serum ECP concentrations 24 hours after allergen challenge was not affected by pretreatment with salmeterol. CONCLUSIONS: A single dose of salmeterol inhibits the allergen induced airway responses and the increase in sputum eosinophils after allergen challenge.

Early increase in urinary leukotriene E4 (LTE4) is dependent on allergen dose inhaled during bronchial challenge in asthmatic subjects.

BACKGROUND: Urinary leukotriene E4 (LTE4) excretion is a good marker of the rate of total body production of sulfidopeptide leukotrienes released during allergen challenge. METHODS: Twenty-three subjects with allergic asthma were challenged with inhaled allergen, and the urinary excretion of LTE4 was determined by immunoenzymatic assay (associated with HPLC separation) at various intervals after challenge. RESULTS: Allergen challenge caused an early airway response (EAR) with a drop in FEV1 of 40.3+/-9.9%. This was associated with an increase in urine LTE4 excretion for 0-3 h after allergen inhalation (296+/-225.25 pg/mg creatinine) in comparison with baseline values obtained during the night before challenge (101.02+/-61.97 pg/mg creatinine). Urinary LTE4 excretion was significantly higher in subjects who inhaled a higher dose of allergen during challenge (LTE4 during EAR: 211+/-192 pg/mg creatinine in subjects with inhaled total dose of allergen <0.1 biologic units; 408+/-223 pg/mg creatinine in subjects with inhaled total dose >0.1 biologic units). All subjects showed a late airway response (LAR) to allergen of different severity, from mild (FEV1 fall: 15-20%) to severe (>30%); no correlation was found between the increase in urine LTE4 excreted during LAR (3-7 h after challenge) and the severity of LAR, but only subjects with severe LAR showed a significant increase in LTE4 during LAR in comparison with baseline value. CONCLUSIONS: A release of sulfidopeptide leukotrienes, as evaluated by urinary LTE4 excretion, can be documented during EAR and LAR to allergen in relation to the dose of inhaled allergen, and it can represent a useful index of the events underlying the airway inflammatory responses during allergen challenge.

Relationship between serum heat-stable neutrophil chemotactic activity during early airway reaction to allergen and the pattern of airway response (early versus late reactions) in asthmatic subjects.

In order to evaluate the relationship between allergen-induced heat-stable neutrophil chemotactic activity (HS-NCA) release during early asthmatic reaction (EAR) and the presence of a late asthmatic reaction (LAR), serum HS-NCA was measured at three serum dilutions (1:5, 1:40, 1:200) during EAR induced by allergen in 26 atopic asthmatics, 13 with isolated EAR and 13 with EAR followed by LAR. HS-NCA was measured using a 48-well microchamber with 5-micron-pore-size nitrocellulose filters, using isolated neutrophils from healthy donors and the leading front technique. Subjects with LAR developed EAR after inhalation of a lower dose of allergen than subjects with isolated EAR. Increase in serum HS-NCA during EAR was significantly higher in subjects with isolated EAR than in subjects with EAR plus LAR at the 1:5 dilution, while it was significantly higher in subjects with EAR plus LAR than in the subjects with isolated EAR at the 1:200 dilution; the 1:40 dilution gave similar results in both groups. Changes in serum HS-NCA during EAR significantly correlated with the maximum decrease in forced expiratory volume in 1 s (FEV1) during LAR: a higher decrease in FEV1 during LAR was associated with a lower increase in HS-NCA at the 1:5 dilution (Spearman's rho = 0.43, rho = 0.03), and with a higher increase in NCA at the 1:200 dilution (Spearman's p = -0.46, p = 0.02). These results can be explained by the 'high-dose-inhibition' phenomenon. Assuming that HS-NCA is associated with mast cell degranulation in the airways after allergen challenge, these findings demonstrate that higher mast cell activation during EAR is present in subjects with a subsequent LAR than in subjects with isolated EAR.

Blood markers of early and late airway responses to allergen in asthmatic subjects. Relationship with functional findings.

We evaluated the relationship between blood markers of mast-cell (plasma histamine and serum level of heat-stable neutrophil chemotactic activity [NCA]) and eosinophil (serum eosinophil cationic protein [ECP]) activation during early airway response (EAR) and late airway response (LAR) to allergen inhalation in 24 asthmatic subjects. After EAR, 14 subjects showed significant LAR (FEV1 fall: > or = 25%), while 10 subjects showed equivocal LAR (FEV1 fall: 15-20%). A significant increase from baseline value was observed in plasma histamine and in serum NCA during both EAR and LAR, while serum ECP significantly increased only during LAR. The sensitivity of different markers to detect significant FEV1 fall during EAR and LAR was low, except for NCA. Changes in blood mediators were similar in both groups with significant and equivocal LAR. There was a significant relationship between the increase in NCA during EAR and the severity of LAR. Stepwise regression between changes in different blood markers showed a significant relationship between histamine increase during EAR and ECP increase during LAR. Thus, serum NCA is a more sensitive marker of EAR and LAR than plasma histamine and serum ECP, and its increase during EAR seems predictive of the severity of the subsequent LAR.

Comparison between peak expiratory flow and forced expiratory volume in one second (FEV1) during bronchoconstriction induced by different stimuli.

To evaluate the sensitivity of peak expiratory flow (PEF), obtained by portable peak flow meter, in detecting mild changes in airway caliber as assessed by forced expiratory volume in 1 sec (FEV1), we studied 184 subjects who underwent different bronchial challenge tests for suspected bronchial asthma. We measured FEV1 and PEF during bronchoconstriction induced by different stimuli: allergen, methacholine, toluene diisocyanate vapors, exercise, or distilled water inhalation; a total of 186 tests were examined. Before and at different times after challenge, FEV1 was measured, and immediately after, PEF was obtained by Mini-Wright or Assess Peak Flow Meter; each time FEV1 and PEF were taken as the best of three satisfactory tracings. The median FEV1 change from baseline value of all steps in the different challenge tests was 7.5% (range: 0-66%). The correlation coefficients between FEV1 and PEF percent changes in different challenge tests were low (Spearman's p: 0.27-0.69), with high scattering of the data. The concordance between classes of percent changes in FEV1 and PEF was also low (Cohen's weighted kappa: 0.28-0.42). In subjects with a FEV1 fall > 15% after challenge, the median PEF change after bronchoconstriction was lower than the corresponding FEV1 change [17% (0-52) vs. 27% (17-66)]. When different cutoff limits of PEF percent change were considered, the sensitivity of PEF to detect a significant change in FEV1 (15 or 20% change) during bronchoconstriction was low; specificity was in general higher than sensitivity. We conclude that PEF and FEV1 changes are poorly related during mild bronchoconstriction induced by different stimuli. The low sensitivity of PEF to detect mild changes in airway caliber may represent a limit in the use of PEF in the day-to-day monitoring of asthma.

Comparison between hypertonic and isotonic saline-induced sputum in the evaluation of airway inflammation in subjects with moderate asthma.

BACKGROUND: Hypertonic saline-induced sputum has recently been used for the evaluation of airway inflammation in asthma. OBJECTIVE: To assess the effect of hypertonicity on airway inflammation. METHODS: We compared the inflammatory cell composition of hypertonic saline-induced sputum with that of isotonic saline-induced sputum in 21 asthmatic subjects and, at baseline and 30 min after each sputum induction, we measured bronchial hyper-responsiveness to methacholine as an indirect marker to detect increased airway inflammation. On two different days, the patients inhaled hypertonic saline (3-5% NaCl) or isotonic saline (0.9% NaCl) for 30 min via an ultrasonic nebulizer, while monitoring FEV1. Sputum was collected for inflammatory cell analysis. RESULTS: There was no difference in inflammatory cell percentages obtained with the two methods. Eosinophils were > 1% in 20 subjects after hypertonic saline and in 16 subjects after isotonic saline, but this difference was not statistically significant. Intraclass correlation coefficients for sputum inflammatory cells obtained with the two methods were +0.642 for eosinophils, +0.644 for neutrophils, +0.544 for lymphocytes and +0.505 for macrophages. Hypertonic saline induced bronchoconstruction in a significantly greater number of subjects than isotonic saline. Also, hypertonic saline increased bronchial responsiveness to methacholine, while isotonic saline did not. CONCLUSION: We conclude that hypertonicity does not affect sputum cell composition, suggesting that inflammatory cells in hypertonic saline-induced sputum are probably preexisting and not acutely recruited in the airways by the hypertonic stimulus. However, the bronchoconstriction and the increase in bronchial hyper-responsiveness after hypertonic saline inhalation may imply the release of inflammatory mediators. This fact must be considered in the evaluation of soluble markers of inflammation in hypertonic saline-induced sputum.

[Clinical pharmacology of leucotriene inhibitors]. / Farmacologia clinica degli inibitori dei leucotrieni.

Leukotrienes have been demonstrated to play an important role as mediators of many pathophysiologic alterations of asthma. Pharmaceutical companies have thus promode many efforts to synthesize new drugs with inhibitory activity on 5-lypoxygenase or with functional antagonism on cystenyl leukotriene receptors. Several compounds have been studied in humans, and some of them should soon be on the market. One of these compounds, ICI 204,219 ("accolate"), a receptor antagonist active by the oral route, has been proven capable of preventing bronchoconstriction induced by several stimuli (allergen, exercise, cold air, etc.) and of improving symptoms and lung function in spontaneous asthma. This effect augments the bronchodilation induced by inhaled beta 2-agonists. On the other hand, no relevant side effects have been reported. However, antiinflammatory properties of this compound must be demonstrated. This new category of antiasthmatic drugs should be recommended for mild-to-moderate asthma, although future studies might demonstrate their efficacy in potentiating or substituting inhaled steroids.

Effect of short-term NO2 exposure on induced sputum in normal, asthmatic and COPD subjects.

The aim of this study was to assess the effects of short-term exposure to low levels of nitrogen dioxide (NO2) on airway inflammation. We studied seven normal, eight mild asthmatic and seven chronic obstructive pulmonary disease (COPD) subjects. All subjects were exposed to air or to 0.3 parts per million (ppm) NO2 for 1 h, with moderate intermittent exercise, on different days and in random order. Before and 2 h after exposure, symptom score and results of pulmonary function tests (PFTs) were assessed. All subjects performed nasal lavage and hypertonic saline (HS) inhalation to collect sputum 2 h after both exposures. Asthmatic subjects had a higher percentage of eosinophils than normal and COPD subjects in HS-induced sputum after air (asthmatics: median 13 (range 0.4-37)%; normals: 0 (range 0-2)%; COPD 1.8 (range 0.1-19)%), whilst COPD patients showed a higher percentage of neutrophils than the two others groups. No significant differences in PFT values or percentages of inflammatory cells were observed in nasal lavage and in HS-induced sputum in normal, asthmatic and COPD subjects after NO2 exposure compared to air exposure, except for a mild decrease in forced expiratory volume in one second (FEV1) 2 h after NO2 exposure in COPD patients. Symptom score showed a mild increase after NO2 exposure both in normal subjects and in COPD patients. We conclude that short-term exposure to 0.3 ppm nitrogen dioxide does not induce an early detectable acute inflammation in proximal airways of normal subjects or of patients with asthma or chronic obstructive pulmonary disease.

Effects of systemic glucocorticosteroids on peripheral neutrophil functions in asthmatic subjects: an ex vivo study.

In 21 asthmatic subjects, several functions of isolated peripheral neutrophils (chemokinesis and chemotaxis toward 10% E. coli; superoxide anion generation after PMA; leukotriene B(4) (LTB(4)) release from whole blood and isolated neutrophtls, before and after different stimuli) were evaluated during an acute exacerbation of asthma, and after 14 - 54 days of treatment with systemic glucocorticosteroids (GCS). During acute exacerbation, superoxide anion generation was higher in asthmatics than in eleven normal subjects (39.2 +/- 14.1 vs. 25.2 +/- 7.3 nmol, p < 0.05); there was a significant correlation between FEV(1) (% of predicted) and neutrophil chemotaxis (r = -0.52, p = 0.04). After treatment, there was no significant change in all neutrophil functions, except for a decrease in neutrophil chemotaxis in subjects who showed an FEV(1) increase > 20% after GCS treatment (from 131 +/- 18 to 117 +/- 21 mum, p = 0.005). Chemokinesis sicantly decreased in all subjects, and the changes significantly correlated with an arbitrary score of the total administered dose of GCS (r = 0.57, p < 0.05). These data suggest that neutrophil activation plays a minor role in asthma, and that treatment with GCS is not able to modify most functions of peripheral neutrophils in asthmatic subjects; chemotaxis seems to be related only to the severity of the asthma and it could reflect the improvement of the disease.

Oral slow-release theophylline does not prevent early and late asthmatic response to allergen in sensitized subjects.

In order to assess whether treatment with oral slow-release theophylline prevents early (EAR) and/or late (LAR) airway responses to allergen, we treated six asthmatic subjects with either placebo or oral theophylline (350 mg b.i.d.) for one week before specific bronchial provocation test (sBPT) with allergen, in a double-blind, cross-over, placebo-controlled study. All subjects had previously shown both EAR and LAR to allergen sBPT. On the day of sBPT, serum theophylline concentration was > 9 micrograms.ml-1 in all subjects treated with theophylline except one (mean 9.8 +/- 2.6 micrograms.ml-1). The total dose (TD) of inhaled allergen, and the provocative dose of allergen causing a 15% fall in forced expiratory volume in one second (PD15FEV1) during sBPT was mildly but significantly lower during theophylline-sBPT than during placebo-sBPT. Theophylline treatment reduced EAR (maximum FEV1 fall from baseline: 26.3 +/- 6.7 vs 32.2 +/- 9.5% after placebo treatment) but not LAR (19.5 +/- 6.5 vs 26.3 +/- 6.1%). A significant protection of LAR (a reduction in FEV1 fall after theophylline treatment 50% more than after placebo treatment) was observed in only 2 out of 6 subjects. Area under the curve was not significantly different after the two treatments. There was no relationship between serum theophylline levels and the degree of protection on EAR or LAR. The decrease in PD15FEV1 methacholine observed at the end of LAR was similar in the two treatments.(ABSTRACT TRUNCATED AT 250 WORDS)

Peak expiratory flow monitoring in diagnosis and management of occupational asthma.

The role of peak expiratory flow (PEF) monitoring in the diagnosis of occupational asthma has recently been assessed by several studies, which agree that this procedure should always be used to confirm the relationship between symptoms and occupational exposure. Some specific issues should be satisfied: a minimum number of four PEF measurements in a day; several weeks of monitoring in and out of work; and the presence of specific patterns of PEF changes. The sensitivity and specificity of PEF monitoring to detect occupational asthma, in comparison with the specific challenge test in the laboratory (the "gold standard") have been shown to be fairly high, although many authors believe that PEF monitoring cannot substitute for the specific challenge test. Limitations include: the low sensitivity of PEF to detect mild changes in airway calibre with respect to forced expiratory volume in one second (FEV1); the blunting effect of pharmacological treatment; the episodic and irregular exposure to the sensitizer in the workplace; and the compliance and honesty of the subject. Further studies are required to select the best indices of daily and day-to-day variability to be used in the evaluation of PEF changes between work and out-of-work periods.

Postallergen inhaled budesonide reduces late asthmatic response and inhibits the associated increase of airway responsiveness to methacholine in asthmatics.

To determine whether inhaled budesonide given after allergen inhalation challenge inhibits the late asthmatic response (LAR) and/or the associated increase of airway responsiveness to methacholine, we performed a double-blind randomized cross-over study in 12 adult asthmatics (eight male, four female; mean age, 20.3 yr; range, 18 to 29 yr) sensitized to Dermatophagoides pteronyssinus (DP) previously shown to develop early and late asthmatic response to allergen challenge with DP. On different days each subject was randomized to receive budesonide 800 micrograms by Turbuhaler or placebo, given three times; (1) after allergen inhalation, after the onset of LAR, when FEV1 had fallen by > or = 15%; (2) 2 h later; (3) 4 h later. Airway responsiveness to methacholine was measured before allergen challenge at 8 to 10 h from allergen inhalation and 24 h after the allergen inhalation. Inhaled budesonide significantly reduced the LAR induced by allergen (maximal % fall in FEV1, delta FEV1%: -23 +/- 6% with budesonide versus -38 +/- 9% with placebo; p < 0.001) and inhibited the associated increase of airway responsiveness (geometric mean of PD20FEV1 methacholine: 0.047 mg after budesonide versus 0.033 mg after placebo at 8 to 10 h, p < 0.05; 0.119 mg after budesonide versus 0.062 mg after placebo at 24 h, p < 0.01). These results suggest that inhaled budesonide may not only prevent but also reduce the late asthmatic response induced by allergen and that it might also be considered in the treatment of exacerbation of asthma.

Prognosis of occupational asthma.

Several studies on the prognosis of occupational asthma have shown that a significant proportion of patients continue to experience asthmatic symptoms and nonspecific bronchial hyperresponsiveness after cessation of work. The determinants of this unfavourable prognosis of asthma are: long duration of exposure before the onset of asthma; long duration of symptoms before diagnosis; baseline airway obstruction; dual response after specific challenge test; and the persistence of markers of airway inflammation in bronchoalveolar lavage fluid and bronchial biopsy. The relevance of immunological markers in the outcome of occupational asthma has not yet been assessed. Further occupational exposure in sensitized subjects leads to persistence and sometimes to progressive deterioration of asthma, irrespective of the reduction of exposure to the specific sensitizer, and only the use of particular protective devices effectively prevents the progression of the disease. A long-term follow-up study of toluene diisocyanate (TDI)-induced asthma showed that the improvement in bronchial hyperresponsiveness to methacholine occurred in a small percentage of subjects and only a long time after work cessation. Bronchial sensitivity to TDI may disappear, but non-specific bronchial hyperresponsiveness often persists unchanged, suggesting a permanent deregulation of airway tone. Steroid treatment significantly reduces nonspecific bronchial hyperresponsiveness only when started immediately after diagnosis.