Chronic productive cough in young adults is very often due to chronic rhino-sinusitis.

BACKGROUND: Chronic productive cough is a common clinical problem; often potential causes outside the lower respiratory tract are forgotten or ignored. The aim of this study was to make a precise etiopathogenetic diagnosis of chronic productive cough in young adults. METHODS: In a clinical setting, 212 subjects (mean age 41+/-5 years) who had reported chronic productive cough in a previous postal survey of a young adult population underwent within two years clinical and functional investigations following a rational diagnostic approach. Two pulmonologists independently established the diagnosis using a clinically structured interview on nasal and respiratory symptoms, spirometry and other tests when appropriate (bronchodilator test or methacholine bronchial challenge, chest radiography); if rhino-sinusitis was suspected, subjects underwent an ENT examination with nasal endoscopy and/or sinus computed tomography. RESULTS: At the end of the diagnostic procedure, 87 subjects (41%) no longer had chronic productive cough and had normal function. Fifty-eight subjects (27%) had chronic rhino-sinusitis; seventeen subjects (8%) had asthma, and of these fourteen also had chronic rhino-sinusitis; 50 subjects (24%) had COPD stage 0+, of these seven also had chronic rhino-sinusitis. Chronic rhino-sinusitis was more frequent in females than in males (p<0.05). CONCLUSIONS: Both in clinical practice and in epidemiological studies, it is important to consider that the origin of chronic productive cough could be frequently outside the lower respiratory tract; a consistent percentage of young adults with persistent productive cough has indeed chronic rhino-sinusitis.

Effects of celiprolol on the bronchial reactivity in asthma.

In 10 patients with bronchial asthma but normal ventilatory function, celiprolol, a cardioselective beta-adrenoreceptor antagonist, did not significantly affect forced expiratory volume in 1 second (FEV1) or airways resistance (Raw). In contrast, metoprolol substantially reduced FEV1 and increased Raw. In addition, compared with metoprolol, celiprolol induced a greater recovery of FEV1 and Raw after methacholine-induced bronchoconstriction.

Lung function abnormalities after bone marrow transplantation in children: has the trend recently changed?

STUDY OBJECTIVES: To evaluate early and late lung function abnormalities and their predictors in a large sample of children who underwent bone marrow transplantation (BMT) for leukemias in the 1990s, highlighting changes with respect to the 1980s. DESIGNS: Prospective cohort. SETTING: A university department of pediatrics. PARTICIPANTS: Seventy-five consecutive children who underwent BMT were enrolled in the study (median age, 11 years; range, 6 to 19 years; 45 male and 30 female children). Twenty-three children received autologous BMT, and 52 children received allogeneic BMT; 50 children completed the study. MEASUREMENTS: Clinical examinations and lung function tests were performed before BMT, and 3 to 6 months, 12 months, and 24 months after BMT. RESULTS: Before BMT, at 3 to 6 months after BMT, and at 24 months after BMT, 44%, 85%, and 62% of children, respectively, had altered lung function in the absence of persistent respiratory symptoms. Between 3 months and 6 months after BMT, a restrictive pattern was the most frequent abnormality. The only predictive factors for late abnormalities were transplantation performed in the advanced disease phase (odds ratio [OR], 6.75; p = 0.005) and bronchopulmonary infections (OR, 3.9; p < 0.05). CONCLUSIONS: These data suggest that a significant proportion of children who undergo BMT, especially if for leukemia in advanced phase, have early and late pulmonary abnormalities. These abnormalities, especially the late ones, seem to be more severe than patients reported in studies analyzing children undergoing BMT in the 1980s. This could be due to the more intensive front-line treatment protocols employed for treatment of children with acute leukemia in the 1990s.

Lung cancer resection: the prediction of postsurgical outcomes should include long-term functional results.

STUDY OBJECTIVES: To assess (1) the possibility of predicting long-term postoperative lung function, and (2) the usefulness of maximal oxygen consumption (O(2)max) as a criterion for operability and as a predictor of long-term disability. DESIGN: Prospective study. SETTING: Outpatients and inpatients of a university hospital. PARTICIPANTS: Sixty-two consecutive patients (mean +/- SD age, 62 +/- 8 years; 51 male and 11 female patients) were preoperatively evaluated for lung cancer resection (pneumonectomy or bilobectomy [n = 14] and lobectomy [n = 48]). MEASUREMENTS: Clinical examination and recorded respiratory symptoms and spirometry results before surgery and 6 months after surgery. If predicted postoperative FEV(1) (ppoFEV(1)) was < 40%, patients underwent exercise testing; if O(2)max was between 10 mL/kg/min and 20 mL/kg/min, patients underwent a split-function study. RESULTS: All the patients with ppoFEV(1) > or = 40%-even those patients (26%) with FEV(1) < 80%-underwent thoracotomy without further tests. Seven patients with ppoFEV(1) < 40% underwent exercise testing, and three of them underwent a split-function study. Nine patients (15%; including six patients with COPD and one patient with asthma) had immediate postoperative complications (pneumonia [n = 5] and respiratory failure [n = 4]); seven of these patients had ppoFEV(1) > or = 40%. ppoFEV(1) significantly underestimated the actual postoperative FEV(1) (poFEV(1); p < 0.001) 6 months after pneumonectomy or bilobectomy but was reliable for actual poFEV(1) after lobectomy. Two patients with predicted postoperative O(2)max > 10 mL/kg/min became oxygen dependent and had marked limitation of daily living. CONCLUSIONS: ppoFEV(1) > or = 40% reliably identifies patients not requiring further tests and not at long-term risk of respiratory disability. O(2)max, effective for defining the immediate surgical risk, is not useful in predicting long-term disability.

Lung function in survivors of childhood acute lymphoblastic leukemia.

STUDY OBJECTIVES: To evaluate lung function in patients cured from childhood acute lymphoblastic leukemia (ALL) with chemotherapy alone or plus bone marrow transplantation (BMT). Pulmonary toxicity is a well-recognized side effect of many ALL treatments. DESIGN: Cross-sectional study conducted at least 3 years after cessation of therapy. SETTING: Outpatient pneumology department of the University Hospital. PATIENTS: Forty-four subjects (age range at observation, 6 to 23 years): 21 treated only with intensive Berlin-Frankfurt-Munster (BFM)-type chemotherapy for newly diagnosed ALL (group A), and 23 treated with chemotherapy plus BMT (group B). MEASUREMENTS: A detailed history of smoking habit, respiratory symptoms, and diseases was recorded directly from the patients with the aid of their parents. A complete physical examination and lung function testing (lung volumes and diffusion capacity for carbon monoxide [DLCO]) were performed in all subjects. RESULTS: No patient reported acute or chronic respiratory symptoms or diseases. In group A patients, lung function was in the normal range, except for three subjects in whom there was an isolated impairment of DLCO. In group B patients, lung function was markedly impaired, with more than half the patients having an abnormal DLCO. A statistically significant difference was found between the two groups for FVC (p = 0.022) and DLCO (p = 0.004). CONCLUSIONS: Intensive, BFM-type frontline chemotherapy is not associated with late pulmonary dysfunction; however, retreatment including BMT can frequently injure the lung. Thus, in patients who undergo BMT and whose life expectancy is long, careful monitoring of lung function and counseling about avoiding additional lung risk factors is recommended.

Distribution of bronchial nonspecific reactivity in the general population.

We investigated 654 subjects of a small Lombardy (Italy) town between 15 and 64 years of age who were representative of the general population. By clinical examination, the sample included 535 normal subjects (164 normal smokers, 341 normal nonsmokers, 30 normal subjects with acute upper respiratory illness within 30 days before the challenge), 50 with chronic bronchitis, 26 with asthma, and 43 with allergic rhinitis. Subjects whose FEV1 was 75 percent or more than the predicted value (654) underwent methacholine bronchial challenge by means of 1 percent metered-dose solution. The test result was considered positive at a drop of more than 15 percent in FEV1 (compared with buffer). Normal smokers and all of the groups with disease had a significantly different distribution of reactivity compared with normal nonsmokers. The difference between asthmatic and these "normal" subjects was highly significant; nevertheless, a clear cut-off between the two groups does not appear to exist.

Breathing patterns and HbSaO2 changes during nocturnal sleep in patients with Duchenne muscular dystrophy.

A night-time polygraphic sleep recording with continuous HbSaO2 monitoring was performed in 11 chair-bound Duchenne muscular dystrophy patients with severe restrictive lung disease but with blood gas values within normal limits when awake. No abnormalities of sleep pattern were detected. Nocturnal sleep did not have significant adverse effects on respiration. However, in 6 patients, infrequent central apnoeas or hypopnoeas occurred which were associated with falls in HbSaO2 greater than those that have been reported to be in normal subjects. The magnitude of HbSaO2 falls appeared to be significantly correlated with functional residual capacity values. Overall, the findings revealed a relatively preserved, although unstable, blood O2 balance during nocturnal NREM and REM sleep in patients with Duchenne muscular dystrophy, even in an advanced stage of their illness.

A clinical, EEG and CT study in 21 cases of chronic respiratory failure.

A clinical, EEG and CT study was carried out on 21 patients with chronic stable respiratory failure. The neurological disturbances and mental deterioration observed were of a mild degree, and no severe alterations were detected at EEG. CT showed cerebral atrophy, but the type and prevalence did not differ substantially between patients studied and normal sex- and age-matched control subjects. The data gave evidence that in chronic stable respiratory failure cerebral function is only slightly affected.

Sleep disorders in neuromuscular diseases.

This article reports the results of several studies on neuromuscular patients (9 Duchenne's muscular dystrophy, 10 myotonic muscular dystrophy, 8 mitochondrial myopathies, 6 spinal muscular atrophy). An evaluation of respiratory function during wakefulness, a sleep questionnaire and an overnight polysomnography were performed in all patients. Recurrent hypoxaemia of variable degree was observed during sleep. In most cases, night-time hypoxaemia appears not to be predictable during wakefulness. Nocturnal hypoxaemia occurs in relation to apnoeas or hypopnoeas, mainly of central type, especially when these breathing irregularities occur during rapid eye movement (REM) sleep. Moreover, polygraphic sleep-apnoea patterns, as defined by international criteria, seem to be an infrequent condition, except for those neuromuscular diseases, characterized by an involvement of the central nervous system.

Respiratory function in precapillary pulmonary hypertension.

Since dyspnoea on exertion is very often the first symptom of precapillary pulmonary hypertension (PPH), either from chronic thromboembolic pulmonary hypertension (CTEPH) or from idiopathic pulmonary hypertension (IPH), these patients are often first examined in a pulmonary function laboratory. We carried out a retrospective study (1987-1992) on pulmonary function in 34 patients diagnosed to have PPH by means of specific diagnostic tools, out of 5,467 patients first attending our laboratory. Nine suffered from IPH, 10 from CTEPH and 15 from Eisenmenger physiology. This last group differed from the others, since its diagnosis had been known for a long time and the stage of the disease was more advanced, when pulmonary function tests were performed in our laboratory (with a view to transplantation). Respiratory function, blood gases and arterial oxyhaemoglobin saturation (HbSaO2) during exercise (Bruce protocol), diffusing capacity of the lungs for carbon monoxide (DLCO), shunt fraction (QS%) (approximation obtained from arterial oxygen tension (PaO2) after 100% oxygen breathing) had been evaluated. In the first two groups, in contrast to other reports, we could observe no obstructive defect. Only 20% of the subjects had restrictive defects, however mild. The typical functional picture of these patients revealed normal lung volumes, normal or slightly reduced DLCO, mild hypoxaemia with hypocapnia, severe HbSaO2 drops during exercise, and pathological QS%. We conclude that every time a patient presents with breathlessness at rest or on exercise, a normal chest X-ray and respiratory function tests, pulmonary hypertension must be suspected and subject to specific and invasive tests. More severe functional impairment was observed in the PPH from the Eisenmenger disorder. This might be due to a more advanced stage of this type of hypertension at the time of our observation and/or to the different mechanisms of the diseases themselves.

Chronic respiratory symptoms, bronchial responsiveness and dietary sodium and potassium: a population-based study.

A possible relationship between Na+ intake and increased prevalence and mortality from asthma and chronic obstructive pulmonary disease (COPD) has been suggested but not clearly proven for several reasons (difficulty in assessing Na+ and K+ both by 24 h excretion and dietary recall, too small an effect of these ions on the pathology, and the role of potential confounders). We wanted to determine the relationship of Na+ and K+ intake, assessed by means of a 7 day recall, with chronic respiratory symptoms and bronchial responsiveness in a sample of the general population. Two hundred and five subjects were studied, with complete dietary and respiratory questionnaires, and baseline respiratory function tests, together with a subsample of 146 subjects who underwent histamine challenge. The 7 day recall consisted of two parts: the first assessed discretionary Na+; and the second assessed Na+ and K+ contained in food. The whole sample was split into two groups based on the levels of consumption, and the statistical analysis was performed contrasting the three lower quartiles vs the highest. Smoking habit, social economic status, age and body mass index (BMI) were not confounders for Na+ and K+ intake. The prevalence of symptomatic subjects and baseline respiratory function values were not significantly different in the two groups of quartiles for Na+ and K+. Baseline respiratory values and dose-response slope of the subsample were also not significantly different. We did not prove a relationship between these dietary factors and either bronchial responsiveness or chronic respiratory symptoms. Although we consider that our questionnaire is more reliable than other methods for Na+ and K+ assessment, several potential biases still remain.(ABSTRACT TRUNCATED AT 250 WORDS)

Prediction of FEV1 reductions in patients undergoing pulmonary resection.

In the assessment of functional operability of lung cancer the simple calculation of predicted postoperative forced expiratory volume in one second (ppoFEV1) based on the number of the bronchopulmonary segments removed, has recently been found to underestimate the actual postoperative forced expiratory volume in one second (FEV1). We checked whether this could be accounted for by lesions causing uneven ventilation or perfusion. We performed a retrospective study of 12 patients with atelectasis, hilar disease or endobronchial involvement (Group A) versus 24 patients with peripheral lung cancer (Group B). Baseline and postoperative FEV1 were measured and ppoFEV1 and ppoFEV1/actual postoperative FEV1 were calculated. In all subjects in Group A ppoFEV1 grossly underestimated the measured postoperative FEV1 (mean (SD) ratio between the two parameters: 67.0 (12.1)%). In Group B, ppoFEV1 was almost identical to the measured value in all but three patients, in whom it only slightly underestimated the actual postoperative value (mean ratio between the two parameters: 94.9 (12.6) %). In conclusion, predicted postoperative forced expiratory volume in one second is useful in the preoperative assessment of patients undergoing lung resection for lesions other than those causing uneven ventilation or perfusion. When this condition is suspected, before declaring a given case ineligible for surgery or at high risk of complications, more sophisticated procedures, such as radionuclide perfusion studies, should be performed.

The efficacy of noninvasive mechanical ventilation on nocturnal hypoxaemia in Duchenne's muscular dystrophy.

The aim of this 2 yr follow-up study was to evaluate the efficacy of nocturnal noninvasive mechanical ventilation in a group of 10 Duchenne's muscular dystrophy (DMD) patients who desaturated during the night but had normal daytime blood gases: mean (range) age 18.3 (15-22) yrs; mean (SD) vital capacity (VC) 752.5 (460-1,308) mL; mean time in bed (TIB) with arterial oxygen saturation (Sa,O2) < 90% 22.8% of total TIB (range: 16.6-32.0); mean arterial oxygen tension (Pa,O2) 10.3 (9.3-11.7) kPa (78 (70.0-87.8) mmHg); mean arterial carbon dioxide tension (Pa,CO2) 5.9 (4.8-6.5) kPa (44.3 (36.3-48.5) mmHg). All the patients were noninvasively ventilated during the night with a bilevel positive pressure ventilation (BiPAP) devise in spontaneous mode in order to correct the episodes of nocturnal desaturation. Nocturnal Sa,O2 values normalized during nocturnal noninvasive mechanical ventilation, and daytime sleep-disordered breathing disappeared, for the entire study period. No statistically significant differences were observed between baseline and follow-up daytime blood gas values, although a slight increase in Pa,O2 was found. During the follow-up, VC declined at a rate of 79.1 +/- 25 mL.yr-1, less than that generally reported in the past in untreated patients in the same age range. In conclusion, our data suggest that patients with advanced Duchenne's muscular dystrophy with pronounced nocturnal desaturation, not fulfilling criteria for imperative ventilation, could be successfully treated with "elective" nocturnal ventilation with immediate benefits consequent to the correction of the nocturnal blood gas anomalies and with long-term benefits related to the preservation of residual respiratory function, delay of development of chronic hypercapnia and thus the requirement for imperative mechanical ventilation.

Pulmonary function in patients with systemic sclerosis.

The lungs are frequently affected in systemic sclerosis (SSc), a generalized connective tissue disorder. We evaluated the prevalence of respiratory functional abnormalities and their correlation with symptoms and radiograph features in a group of 34 patients who fulfilled the American Rheumatism Association criteria for the diagnosis of systemic sclerosis. Patients were submitted to a specific respiratory questionnaire and to lung function tests. Measurements were performed according to the European Coal and Steel Community (ECSC) recommendations and results expressed as a SD score, an accurate method that, taking into account the dispersion of the parameters in the reference population, allows precise definition of pathological subjects. Of the patients examined, 38% reported dyspnoea at rest or on exertion. No other respiratory symptoms were reported. Fifty percent had a normal chest radiograph. This study documents the high prevalence of respiratory functional abnormalities in patients with SSc. A restrictive pattern was found in 41% and an isolated diffusion impairment in 18%. No significant relationship was found between the isolated impairment of transfer factor of the lungs for carbon monoxide (TL,CO) and the mean duration of the scleroderma: thus, it does not seem to represent an early sign of severe restrictive disease. No bronchial or bronchiolar obstructive patterns were observed: it can be stated that small airways dysfunction is not a characteristic manifestation of SSc as considered previously. A significant association was found between the group of subjects with chest radiographic abnormalities and that with a restrictive pattern or isolated TL,CO alteration (p = 0.018). Chest radiographic abnormalities were also found in 29% and dyspnoea in 35% of the patients with normal respiratory function. The mean duration of scleroderma was not significantly different between the groups with and without abnormalities on chest radiography, between the groups with and without a restrictive pattern or isolated diffusion impairment, and between the groups of patients with and without dyspnoea. In conclusion, an accurate evaluation of respiratory function is recommended in the assessment of patients with systemic sclerosis, since the functional involvement of the lung cannot be predicted on the basis of the chest radiograph and the respiratory symptoms.

[Cigarette smoke and bronchial hypersensitivity]. / Fumo di sigaretta e iperresponsività bronchiale.

Among intrinsic factors which may affect the onset of COPD, bronchial non specific hyperresponsiveness seems to play an important, even though, ill-defined role. Attention is drawn to 2 major points: 1) Cigarette smoking habit may increase airway responsiveness? 2) Any possible hyperresponsiveness induced by smoking may be relevant in the development of COPD? At present, only point 1 may be positively answered; point 2 will be clarified by means of perspective and long-term surveys, we have not achieved yet. Our cross-sectional study showed a significant influence of smoking on bronchial responsiveness in absolutely asymptomatic subjects and with airway caliber absolutely in the normal range. This kind of influence resulted to be dose-dependent. Furthermore a noxious role of smoking has been observed, the greater effect the higher amount of cigarettes/day smoked. Moreover this acute role of smoking has been remarked by the trend of bronchial responsiveness of past-smokers, the more similar to non smoker's, the more far was smoking cessation.

Effects of inhaled steroids on methacholine-induced bronchoconstriction and gas trapping in mild asthma.

According to a recent hypothesis, airway smooth muscle regulates airway calibre mostly at high lung volume, whereas the mucosa and adventitia dimensions dominate at low lung volumes. It was thought that if inhaled steroids decrease the thickness of airway wall in asthma, then forced vital capacity (FVC), which reflects the functional changes at low lung volume, should decrease less during induced bronchoconstriction than flow at high volume. The study was conducted in 31 mild asthmatics under control conditions and during a methacholine challenge before and after 4-weeks treatment with inhaled fluticasone dipropionate (1.5 mg daily, 16 patients) or placebo (15 patients). After fluticasone dipropionate treatment, control forced expiratory volume in one second (FEV1), and maximal flow at 50% of control FVC during forced expiration after a maximal (V'max,50) and a partial inspiration (V'p,50) significantly increased. During methacholine challenge, FVC decreased less than did FEV1 or V'max,50, and so did inspiratory vital capacity compared to V'p,50. Both the provocative dose of methacholine causing a 20% fall in FEV1 and the bronchodilator effect of deep inhalation significantly increased. The latter was assessed by means of the regression coefficient of all V'max,50 plotted against V'p,50. No significant changes in these parameters occurred after placebo. These data show that inhaled steroids remarkably blunt the occurrence of gas trapping during induced bronchoconstriction in mild bronchial asthma, possibly due to their effect on airway wall remodelling.

International variations in asthma treatment compliance: the results of the European Community Respiratory Health Survey (ECRHS).

Noncompliance to medication is a major barrier to effective asthma management. Its real extent and geographical variation throughout the world are not yet known. The data on compliance, collected in the framework of the European Community Respiratory Health Survey (ECRHS) on 1771 subjects (aged 20-44 yrs) with current asthma identified in 14 countries, offer a unique opportunity to assess the extent of noncompliance and its variation across countries. The median percentage of current asthmatics who had received a medical prescription at least once was 95%. The compliance of those patients who had received a medical prescription was found to be low in all countries (median 67%) but with wide variations, the rate ranging from 40% (USA) to 78% (Iceland). During exacerbations patients' rate of compliance increased to 72%. Age was the only variable which influenced compliance to treatment. A significant, although weak, negative correlation was found between patients' compliance and rate of hospital casualty department or emergency room admissions. This study documents that compliance to the treatment of asthma is poor worldwide and that there are large variations between countries. These results emphasize the necessity for further efforts to improve patients' education and to promulgate the international guidelines.

Epidemiological diagnosis of asthma: methodological considerations of prevalence evaluation.

Within an epidemiological survey on Chronic Obstructive Pulmonary Disease, before reporting data on the prevalence of bronchial asthma we checked the group of subjects defined as "pathological" by means of a suitable questionnaire and a group of "normals" as a control. We evaluated the sensitivity and specificity of the questionnaire, in comparison with a clinical evaluation made by two physicians and controlled the relationship among their results, non-specific bronchial hyperreactivity and skin tests. In particular the correspondence between diagnosis made by physicians from a clinical evaluation and that obtained by questionnaire was not satisfactory. We suggest the importance of employing physicians for an epidemiological approach to asthma, in absence of a valid objective criterion.

A comparison of the bronchodilator effects of broxaterol and salbutamol.

In 12 adult patients with reversible bronchospasm (7 bronchial asthma and 5 chronic obstructive bronchitis) the bronchodilator activity and tolerability of 200 and 400 mcg of broxaterol hydrochloride (Z 1170) were compared to those of 200 mcg of salbutamol administered by metered-dose inhaler. A single dose of the drugs was compared in a double-blind balanced latin square cross-over design. FEV1, FVC, MMEF, MEF25, heart rate and blood pressure were measured just before and 7.5, 15, 30, 60, 120, 180 and 240 min after each treatment. At these times clinical evaluation was also carried out to ascertain the presence of side effects. In the doses employed, broxaterol and salbutamol caused significant increases over baseline FEV1, MMEF and MEF25 from 7.5 to 240 min and FVC from 7.5 to 120 min. The difference between the effects of the two doses of broxaterol on FVC, MMEF and MEF25 was significant at 15 min. No significant difference was observed in the activity curves of 400 mcg of broxaterol and salbutamol. The effects of salbutamol were significantly greater than those of 200 mcg of broxaterol on FEV1 at 7.5 and 15 min and on FVC, MMEF and MEF25 at 15 min. All three treatments were well tolerated. No significant changes were observed in heart rate or blood pressure and tremors were not reported in any patient.

Bronchial responsiveness to inhaled methacholine in epidemiological studies: comparison of different indices.

We evaluated the sensitivity and specificity of different indices drawn from the forced expiratory curve in order to detect the best one for evaluating bronchial reactivity in the general population, and particularly, for distinguishing between normal and asthmatic subjects. 654 subjects, between 15 and 64 years of age, who were representative for age and sex of the general population of a small Lombardy town (Italy), were studied. Of the total sample, 448 subjects were clinically normal and asymptomatic, 87 were symptomatic or with acute upper respiratory disease within 30 days before the challenge with methacholine, 43 with allergic rhinitis, 26 asthmatics and 50 chronic bronchitics. All the subjects who had a baseline FEV1 greater than 85% predicted underwent methacholine challenge. Provocative LnDoses of a 6, 10, 15% fall in FEV1 (LnPD6, LnPD10, LnPD15) and provocative LnDose causing FEV1 to fall more than 2 SD below the mean of 5 FEV1 measurements following buffer inhalation (LnTD) were evaluated. Furthermore we calculated the "Dose-Response slope" (SL) proposed by O'Connor. The cut-off value of each index to define a responder was calculated by discriminant analysis of the response to the challenge in normal and in the asthmatic group. Sensitivity, specificity and predictive value of LnPD6, LnTD and SL were 79, 74, 14%; 71, 74, 13% and 46, 97, 48% respectively. LnPD10 had the best sensitivity (83%) with a high specificity (83%), but, as compared to LnPD15, whose sensitivity was 79% and specificity 89%, a lower predictive value (21% vs 27%).(ABSTRACT TRUNCATED AT 250 WORDS)