Rare earths and trace elements contents in leaves: A new indicator of the composition of atmospheric dust.

The relationship between the trace element distribution in atmospheric particles and leaves of some exposed plants in the environment was recently demonstrated. This indication would suggest that the trace element analysis of leaves in these plants could provide information about the composition, nature and origin of the atmospheric dust dispersed in the environment. In order to corroborate this hypothesis, the distribution of trace elements and Rare Earths were studied in leaves of some endemic plants, in the atmospheric fallout and in soils of rural, urban and industrial ecosystems in Sicily. These elements have been chosen to discriminate the source and nature of different source on atmospheric dust and the larger capability of the composition of the latter materials to influence the metal ion distribution in leaves of studied plants rather than the soil composition. These evidences are related to the recognition both of positive La anomaly and trace element enrichments in studied leaves and to their particular V/Th and Co/Ni signature. On the other hand, some particular normalised REE features recognised in leaves suggest that a limited contribution to the REE budget in studied leaves is provided by the REE migration from roots.

Concentration and reference interval of trace elements in human hair from students living in Palermo, Sicily (Italy).

Trace element contents in specimens of hair collected from 137 children aged 11-13 years old, living in Palermo (Sicily, Italy) were determined by ICP-MS. This work reports analytical data for the following 19 elements: Al, As, Ba, Cd, Co, Cr, Cu, Li, Mn, Mo, Ni, Pb, Rb, Sb, Se, Sr, U, V and Zn. The most abundant chemical elements were zinc and copper (Zn > Cu), with concentrations exceeding 10 µg/g (Zn = 189.2 µg/g; Cu = 22.9 µg/g). Other elements with concentrations greater than 1 µg/g were, in order of abundance, Al>Sr>Ba>Pb. The remaining elements were all below 1 µg/g. The average elemental concentrations in hair were statistically compared by Kolmogorov-Smirnov's test taking children's gender into account. Al, Ba, Cr, Li, Rb, Sb, Sr, V and Zn were statistically different according to gender, with significance p < 0.001. This study thus confirms the need for hair analysis to differentiate female data from those of males. IUPAC coverage intervals and coverage uncertainties for trace elements in the analysed hair samples are also reported.

Assessment of exposure to environmental tobacco smoke in young adolescents following implementation of smoke-free policy in Italy.

We investigated acute and chronic exposure to environmental tobacco smoke (ETS) in a cohort of young adolescents using urinary cotinine and hair nicotine testing after recent implementation of Italian smoke free legislation. Study subjects were 372 Italian young adolescents, between 10 and 16 years of age from the principal city of Sicily, Palermo. Urine and hair samples were collected between November 2005 and May 2006, when the legislation to ban smoking in all the enclosed places of employment (including bars, restaurants, pubs) was completely enforced. An exhaustive questionnaire including sociodemographic characteristics and active and passive exposure to cigarette smoking was completed. Urinary cotinine was analyzed by radioimmunoassay and hair nicotine by a validated GC/MS method. Based on urinary cotinine results, 2.1% and 89% of the study participants, respectively, showed non-exposure and low acute exposure to ETS, whereas only 1.6% presented very high exposure or a hidden active smoking habit in the recent past. Hair nicotine disclosed non-exposure and low exposure to ETS in 11.8% and 65.6% of the young adolescents, respectively, taking into consideration a larger time-window. High repeated exposure, suggesting active smoking in some cases was observed in 8.6% of the study subjects. Hair nicotine was inversely related to educational level of the adolescents' parents. Overall, due to the implementation of smoke-free legislation and information campaign against smoking, a significant trend toward low exposure to ETS was observed in this study cohort with no association between exposure to ETS and respiratory illnesses.

Bronchial hyperresponsiveness in children with atopic rhinitis: a 7-year follow-up.

BACKGROUND: A high prevalence of bronchial hyperresponsiveness (BHR) was found in atopic subjects with rhinitis. Those subjects may be at higher risk for developing bronchial asthma. We evaluated, in a 7-year follow-up, BHR and atopy in a homogeneous population of nonasthmatic children with allergic rhinitis (AR), and their role in asthma development. METHODS: Twenty-eight children (6-15 years) with AR were studied. At enrollment (T(0)), skin tests, total serum IgE assay, peak expiratory flow (PEF) monitoring and methacholine (Mch) bronchial challenge were performed. BHR was computed as the Mch dose causing a 20% forced expiratory volume (FEV)(1) fall (PD(20)FEV(1)) and as dose-response slope (D(RS)). Subjects were reassessed after 7 years (T(1)) using the same criteria. RESULTS: At T(0), 13 children (46%), showing a PD(20)FEV(1) <1526 microg of Mch, had BHR (Mch+), although PEF variability (PEFv) was within normal limits. None of the children with negative methacholine test developed bronchial asthma after 7 years. Of the 13 Mch+, only two reported asthma symptoms after 7 years. No significant change was seen in the other parameters of atopy considered. CONCLUSION: Children with allergic rhinitis present a high prevalence of BHR. Nevertheless, their PEFv is normal and the rate of asthma development low.

Nocturnal asthma and gastroesophageal reflux.

Bronchial asthma is a complex disease involving various cyclic environmental and chronobiologic factors. In patients with asthma, nocturnal gastroesophageal reflux (GER) has been associated with triggering and worsening bronchoconstriction. There are data to suggest that the prevalence of GER is higher in patients with asthma than in the general population and that GER is directly associated with asthma severity. However, the role of GER in asthma remains controversial; some studies suggest that reflux does not mediate nocturnal asthma symptoms. This article reports the results from a study conducted in 7 adult patients affected by nocturnal asthma and moderate to severe GER disease. The relation between GER and asthma was tested by continuously and simultaneously monitoring respiratory resistances and esophageal pH. The study demonstrated a significant correlation between lower respiratory resistances and spontaneous GER. More specifically, both long (more than 5 minutes' duration) and short (5 minutes' or less duration) GER episodes elicited bronchoconstriction in patients with asthma who had moderate to severe GER disease. The severity and duration of bronchoconstriction were related to the duration of GER.

Changes in FVC during methacholine-induced bronchoconstriction in elderly patients with asthma: bronchial hyperresponsiveness and aging.

STUDY OBJECTIVE: We evaluated whether aging may produce changes in bronchial hyperresponsiveness, risk of enhanced bronchoconstriction, and changes of bronchoconstriction perception. SETTING: Each subject underwent a methacholine bronchial challenge. Methacholine challenge was stopped when one of the following conditions occurred: (1) plateau of bronchoconstriction; (2) decrease of FEV(1) > 40%; (3) FEV(1) drop below 1 L; or (4) excessive respiratory discomfort. Methacholine dose-response curves were plotted both for FVC and FEV(1). The provocative dose of methacholine causing a 20% decrease in FEV(1) with respect to baseline (PD(20)) and the fall in FVC (DeltaFVC) at PD(20) were computed. The Borg scale was used for scoring the perception of respiratory discomfort. PATIENTS: We compared 17 young asthmatic patients (aged 22 to 45 years) with 17 older asthmatic patients (aged 63 to 78 years) selected on the basis of similar baseline pulmonary function and disease duration. RESULTS: No significant between-group difference was found in PD(20) and in plateau development. Conversely, DeltaFVC was significantly higher in the older group (mean +/- SD, 15.5 +/- 3.9% vs 11.6 +/- 5.5% in younger patients). In addition, DeltaFVC showed a positive linear relationship with age (p = 0.0026). Elderly subjects were less aware of bronchoconstriction during the methacholine challenge (p = 0.04). CONCLUSIONS: In elderly patients with asthma having comparable pulmonary function and disease duration, bronchial responsiveness is not different from that observed in younger asthmatic patients. Nevertheless, in such patients, an age-related tendency to an enhanced bronchoconstriction and a reduced perception of the degree of bronchoconstriction exist.

Prevalence of nocturnal asthma in a general population sample: determinants and effect of aging.

Nocturnal asthma (NA) is important because of clinical and prognostic implications. Previous data on prevalence may be overestimated, because they are derived from selected series. Observations on monitoring of peak expiratory flow in elderly asthmatics suggested that prevalence of NA may increase with age. This study was designed to estimate the prevalence of NA-related symptoms in a sample drawn from a general population and evaluate the role of aging. Subjects (1,100, mean age 41.9, SD 22.8 years) were randomly selected from the lists of seven general practitioners. A questionnaire on nighttime and morning NA-associated symptoms was used and frequency of occurrence was rated as never, sometimes (less than once a week), and often (once a week or more). In the overall sample, symptoms were experienced "sometimes" by 2.3%-4.9% of subjects, whereas the response "often" was given by 0.9%-1.6% of subjects. Among subjects with a diagnosis of asthma, symptoms occurred sometimes in 16.7%-23.7% and often in 5%-15%. Symptoms reported the morning after were significantly more frequent among patients aged 65 years and older (p < 0.005), whereas the difference for nighttime symptoms was not statistically significant in different age groups, confirming an age-related blunted sensitivity. Logistic regression analysis shows that a diagnosis of asthma is the most important correlate of symptoms, with odds ratio (OR) up to 14.78 for cough; advanced age also proved to be an independent risk factor (OR 3.35-4.97). In conclusion, although the prevalence of NA was previously overestimated, our results indicate its importance, particularly among elderly patients who are exposed to a prominent risk of underdiagnosis and undertreatment.

Spontaneous gastroesophageal reflux and airway patency during the night in adult asthmatics.

Controversies still exist on the role of nighttime gastroesophageal reflux (GER) in precipitating nocturnal asthma. We tested the relationship between GER and nocturnal bronchoconstriction by continuously and simultaneously monitoring both respiratory resistances and esophageal pH in seven asthmatics with moderate to severe GER disease. Twenty-nine GER episodes were found during the study night lasting more than 5 min (LGER) and 72 not longer than 5 min (SGER). Both long (LGER) and short (SGER) gastroesophageal refluxes were able to maintain significantly higher lower respiratory resistances (RLR) at the resolution of each GER episode (RLR(e)) with respect to baseline values. RLR, expressed as the area under the RLR curve along each GER episode (AUCR(LR)) and as RLR(e), showed significant correlations with GER duration. Moreover, a significant correlation was found between RLR measured 10 min after GER resolution and GER duration during each episode. We conclude that GER itself is able to elicit nocturnal bronchoconstriction in asthmatics with moderate to severe GER disease and that bronchoconstriction severity and duration are related to GER duration.

Respiratory energetics during exercise at high altitude.

The purpose of this study was to assess the effect of high altitude (HA) on work of breathing and external work capacity. On the basis of simultaneous records of esophageal pressure and lung volume, the mechanical power of breathing (Wrs) was measured in four normal subjects during exercise at sea level (SL) and after a 1-mo sojourn at 5,050 m. Maximal exercise ventilation (VEmax) and maximal Wrs were higher at HA than at SL (mean 185 vs. 101 l/min and 129 vs. 40 cal/min, respectively), whereas maximal O2 uptake averaged 2.07 and 3.03 l/min, respectively. In three subjects, the relationship of Wrs to minute ventilation (VE) was the same at SL and HA, whereas, in one individual, Wrs for any given VE was consistently lower at HA. Assuming a mechanical efficiency (E) of 5%, the O2 cost of breathing at HA and SL should amount to 26 and 5.5% of maximal O2 uptake, whereas for E of 20% the corresponding values were 6.5 and 1.4%, respectively. Thus, at HA, Wrs may substantially limit external work unless E is high. Although at SL VEmax did not exceed the critical VE, at which any increase in VE is not useful in terms of body energetics even for E of 5%, at HA VEmax exceeded critical VE even for E of 20%.

Effect of age upon airway obstruction and reversibility in adult patients with asthma.

OBJECTIVE: In a cross-sectional study we evaluated the effect of aging (separately from that of duration of disease) on airway obstruction and reversibility by comparing two groups of non-smoker patients with asthma. METHODS: We compared two groups of patients: group A, which had 50 subjects (8 men and 42 women) aged 59.7+/-4.6 years (mean +/- SD), and group B, comprised of 51 subjects (19 men and 32 women) who were 35.7+/-7.4 years old. The groups were selected because of comparable baseline degree of obstruction (FEV1 % of predicted, 67.8+/-20.3 in group A; 73.0+/-19.6 in group B, NS) and duration of the disease (14.0+/-11.7 years vs 11.2+/-9.1, NS). Spirometric examination, with a bronchodilator test, was performed and subjects not reaching 85% of predicted were submitted to a 4-week course of inhaled steroids. RESULTS: Although a higher number of subjects from group B responded to the acute bronchodilator test (p < 0.001), the maximum response achievable with treatment (steroid or bronchodilator) (deltaFEV1 expressed as the percent of predicted) was not statistically different between groups (12.0+/-17.5 vs 16.0+/-23.9). The mean FEV1 attainable after treatment (deltaFEV1%PT) was significantly lower in the older group (p = 0.0006). Within groups, the baseline FEV1% did not correlate with age; it was inversely correlated with the duration of the disease (p < 0.03 and p < 0.01, respectively). In both groups deltaFEV1 was inversely related with the baseline FEV1, whereas FEV1%PT was correlated with the duration of the disease, with a slope nearly doubled in group B (p < 0.001). CONCLUSIONS: Both the process of aging and the prolonged exposure to disease effects are important factors in determining the functional characteristics of chronic asthma: In particular, aging is associated not only with a reduced acute responsiveness to bronchodilators, but also with a reduced slope of the duration-FEV1%PT relationship that suggests a slowing of the rate of loss of reversibility of uncertain biological meaning.

Effect of ageing on peak expiratory flow variability and nocturnal exacerbations in bronchial asthma.

The aim of this study was to evaluate the role of ageing on variability of airflow obstruction and on the specific pattern of nocturnal exacerbations ("morning dipping" of peak expiratory flow (PEF)) in asthma. Two groups of stable asthmatics (Group A: 23 patients, aged 14-47 yrs; Group B: 20 patients, aged 53-74 yrs), that were similar for duration of disease, degree of obstruction and response to bronchodilators, were studied. PEF was monitored four times daily for 2 weeks, and amplitude of variation and "morning dip" were calculated. Both PEF amplitude and "morning dip" were greater in the older patients (p<0.005). Amplitude was negatively correlated with baseline forced expiratory volume in one second (FEV1) in both groups (p<0.01); multiple correlation with age, duration of disease, baseline FEV1 and degree of reversibility was significant in the older group only. Morning dip was inversely correlated to baseline FEV1 (p<0.01) and reversibility (p<0.05). Nocturnal symptoms were reported by all of the five Group A "dippers", but by only 6 of the 13 Group B "dippers" (p<0.04). Ageing contributes to increased variability of airway calibre in asthma. Aged patients are potentially at risk because functional evidence of nocturnal asthma may frequently be accompanied by a poor subjective awareness. Therefore, a more extensive practice of PEF monitoring is recommended in aged asthmatics.

Evaluation of diaphragmatic fatigue in obstructive sleep apnoeas during non-REM sleep.

BACKGROUND: Resistive load applied to the airways may induce diaphragmatic fatigue, and hypoxaemia has been shown to predispose to the development of fatigue. Inspiratory muscle fatigue may occur in patients with obstructive sleep apnoea syndrome (OSAS), as these patients repetitively develop both inspiratory loading and hypoxaemia. The results of previous studies on this topic are inconclusive, probably because of the methodological approaches used. METHODS: Six obese patients with OSAS underwent a polysomnographic study. The diaphragmatic pressure time index (PTI) was evaluated as an indicator of diaphragmatic contraction, and the mean frequency of the diaphragmatic electromyogram power spectrum (Fm) and the maximum relaxation rate of transdiaphragmatic pressure (MRR) as indices of a fatiguing diaphragm. A total of 119 randomly selected apnoeas (each including 5-13 occluded efforts) were analysed throughout the night in non-REM sleep to assess possible muscle fatigue due to the high pressure generation in each apnoea. A breath-by-breath within-apnoea analysis was performed on the first three pre-apnoeic breaths, on all the occluded efforts, and on the first three unoccluded breaths following the apnoea interruption. Possible fatigue development due to the cumulative effect of apnoeas over the night was also evaluated. RESULTS: A progressive increase of Fm and MRR was found during the obstructive phase in all the subjects in the within-apnoea analysis. The overnight analysis did not show a reduction in either PTI, Fm, or MRR secondary to recurrent upper airway obstruction during the night. CONCLUSIONS: No evidence of diaphragmatic fatigue or impaired diaphragmatic contraction was found either within each apnoea or throughout the whole night, despite the generation of high PTI values during the apnoeic occluded phases. It is concluded that diaphragmatic fatigue does not occur in OSAS during non-REM sleep.

[Variability of managerial and clinical decisions in mental health services of the Lombardy Region: the vignette method]. / Variabilità delle decisioni gestionali e cliniche nei servizi di salute mentale della Regione Lombardia con il metodo delle vignette.

UNLABELLED: This paper concerns one of the four research projects developed during a training course in clinical epidemiology managed by the Lombardy training centers IREF. OBJECTIVES: To compare the recommendations for treatment concerning 9 vignettes derived from the Australian Quality Assurance Project. SETTING: Six Mental Health Services of Regione Lombardia. DESIGN AND PARTICIPANTS: For each vignette, all psychiatrists working in the 6 Mental Health Services were asked to fill in a questionnaire about treatment location, psychopharmacology, psychotherapy, priority between psychotherapy and psychopharmacology and degree of difficulty in answering. RESULTS: 44 out of 52 target psychiatrists took part to the study. Remarkable variability for treatment location and psychotherapies; moderate variation for psychodrugs prescriptions and a good agreement for diagnoses were observed. In drugs prescription an access of association was observed. The most prevalent model of psychotherapy was the psychodynamic, followed by the cognitive-behavioural and the family-systemic. There was a tendency toward a flexible approach, as suggested by recommendations of different psychotherapeutic models according to the nature of the disorder. No case were judged very difficult; only in 3 cases a judgement of "somewhat difficult" was expressed by more than 20% (but less than 30%) of the psychiatrists. CONCLUSIONS: Studies of this type are very easy to carry out and give useful information for continuous training programs and Continuous Quality Improvement projects.

Respiratory mechanics during exhaustive submaximal exercise at high altitude in healthy humans.

1. The present investigation was conducted to test the hypothesis that the respiratory system is stressed more during exhaustive exercise in chronic hypoxia than in normoxia. 2. Four healthy male subjects (aged 33-35 years) exercised on a cycle ergometer at 75% of the local maximum oxygen consumption (Vo2,max) until exhaustion, at sea level (SL) and after a 1 month stay at 5050 m (HA). 3. Airflow at the mouth (V), oesophageal (Po) and gastric (Pg) pressures were measured at rest, during exercise and recovery. Minute ventilation (VE), respiratory power (Wresp), respiratory frequency (f) and transdiaphragmatic pressure (Pdi) were calculated from the measured variables. 4. The subjects' mechanical power output of cycling at HA was 23.7% lower than at SL. In spite of this reduction, time to exhaustion at HA was 55.3% less than at SL. VE increased slightly during exercise at SL, but showed a marked increase at HA, and at the end of exercise at HA was 47.3% higher than at SL. 5. Respiratory power increased more at HA than at SL (77.3% higher at the end of exercise) due to the increase in f needed to sustain the high VE. 6. Gastric pressure swings were negative at the end of HA exercise but always positive at SL. The Pai:Po ratio reached values below 1 at HA but never at SL. 7. These data seem to indicate that the respiratory system is stressed more during submaximal exercise at HA than at SL. We suggest that the exceedingly high VE demand, requiring an excessive Wresp, may lead to fatigue of the diaphragm.

Evaluation of nocturnal bronchoconstriction by all night tracheal sound monitoring.

BACKGROUND: A study was undertaken to evaluate the reliability of a digital tracheal sound analyser (ELENS-DSA) in predicting nocturnal changes in airways resistance in asthmatic patients. This device allows continuous measurement of the proportion of the time occupied by wheezing (Wh%). METHODS: Nocturnal polygraphic studies with simultaneous continuous monitoring of tracheal sounds and airways resistance were performed in seven patients with nocturnal asthma. In order to evaluate the possible bias in wheezing estimation, each tracheal sound recording was passed through the automatic analyser and simultaneously monitored with earphones by an experienced observer. RESULTS: The device detected audible wheezing with an optimal sensitivity and specificity of 70%. Snoring was a minor cause of the relatively poor characteristics of the system. A close correlation (p < 0.001) between Wh% and airways resistance was observed only in those patients with the highest increase in resistance; when the results of all the subjects were pooled the correlation observed was poor. The predictive value of Wh% in detecting changes in airways resistance during 10 minute intervals was lower than 70%. The positive and negative predictive values of Wh% were raised to 79% and 83%, respectively, for 30 minute intervals. CONCLUSIONS: The ELENS-DSA system is a relatively crude means of detecting wheezing and assessing bronchoconstriction quantitatively. However, it is able to detect accurately nocturnal bronchoconstriction for 30 minute intervals. This finding, along with the fact that the monitoring is non-invasive, suggests that it may be a promising tool, especially for patients during sleep.

Urinary leukotriene E4 in the assessment of nocturnal asthma.

BACKGROUND: Urinary leukotriene E4 (LTE4) is a marker of the body's production of cysteinyl LTs, important mediators of airway inflammation. The role of the latter in nocturnal asthma is a topic of increasing interest. OBJECTIVE: This investigation was aimed at determining whether nighttime attacks are associated with increased release of LTs, expressed by urinary LTE4, and the relationship between the two phenomena. METHODS: Three groups were studied: group A, seven control subjects; group B, nine asthmatic patients without nocturnal attacks; and group C, nine asthmatic patients with a comparable daytime FEV1 but who were experiencing nocturnal exacerbations (morning dips in peak expiratory flow greater than 20%). Urine was collected over 24 hours in three samples (9:00 AM to 3:00 PM; 3:00 PM to 9:00 PM; and 9:00 PM to 9:00 AM). LTE4 was measured by high-performance liquid chromatography and radioimmunoassay and expressed as nanograms per millimole of creatinine. RESULTS: No significant differences between urinary LTE4 were noticed within groups A and B. Conversely, in group C urinary LTE4 at night (geometric mean with 95% confidence interval; 35.16 with 28.77-42.85) was significantly higher than that of the other samples (respectively 23.12 with 17.78-30.06, p less than 0.05; and 25.18 with 21.03-30.13, p less than 0.02); it was also significantly higher than in all the samples of other groups. A significant (p less than 0.02) linear correlation was observed between morning dip in peak expiratory flow and the log urinary LTE4 in the nocturnal sample. CONCLUSION: These results indicate the role of LTs in nocturnal asthma and suggest that urinary LTE4 may be a useful marker of this condition.

Ventilatory response to spontaneous resistive load variations during sleep.

We investigated the ventilatory response to spontaneous changes in resistive load during sleep in nine adult asthmatic patients, four of whom were snorers. All patients had a history of nocturnal worsening of respiratory symptoms and were submitted to a nocturnal polysomnographic study in a sleep laboratory. During the night, all patients showed spontaneous increases in pulmonary resistance due to bronchoconstriction. A temporary additional increase in inspiratory resistance (RI) was observed as a result of snoring. In all patients, a highly significant inverse linear relationship was found between ventilation (VE) and RI, but the slopes of the regressions varied considerably among patients; the decrease in VE was due to a reduced mean inspiratory flow. The most effective ventilatory compensation to increasing resistive load (lowest absolute values in the VE/RI slopes) was observed in two patients: one nonsnorer and one snorer. Effective VE compensation appeared to be dependent on the individual's combined adjustments of transpulmonary pressure (Ptp) and duty cycle (TI/TT). In fact, an increase in Ptp, linearly related to RI, was observed in all patients except one (a snorer during nonsnoring breathing); however, the Ptp increase was able to compensate VE only when TI/TT increased. We conclude that, in sleeping asthmatic patients, VE adaptation to increased spontaneous load is highly variable among patients and its effectiveness is related to individual strategies on the basis of adequate adjustments of neuromuscular output and timing of the breathing cycle.

Relationship of nocturnal bronchoconstriction to sleep stages.

The possible role of sleep stages in the pathogenesis of nocturnal asthmatic attacks is still under debate because previous studies suffered methodologic limitations that prevented the possibility of providing a clear-cut answer to the question. To evaluate the relationship of nocturnal asthma to sleep, eight asthmatics with unstable asthma (seven with history of nocturnal wheeze) and four reference subjects were submitted to all-night polysomnography, including the continuous evaluation of esophageal and supraglottic pressure (with two catheters) as well as of airflow (with a face mask), so as to derive total lung resistance, supraglottic resistance, and, by subtraction lower respiratory resistance (Rlr). Stage 3-4 was characterized by the highest peaks in Rlr and by longer episodes of bronchoconstriction; conversely, neither the onset nor the remission of the latter were specifically related to any sleep stage. Considering episodes remitted with an awakening. Stage 3-4 was marked by higher Rlr peaks than during REM sleep. We conclude that sleep plays a contributory role in the multifactorial pathogenesis of nocturnal asthma, with a higher susceptibility during slow-wave sleep, probably related to a decreased responsivity to resistive loads.