Phenotyping OSAH patients during wakefulness.

PURPOSE: Although currently there are simplified methods to measure the pathophysiological traits that stimulate the occurrence and maintenance of obstructive sleep apnea-hypopnea (OSAH), they remain difficult to implement in routine practice. This pilot study aimed to find a simpler daytime approach to obtain a meaningful, similar pathophysiological phenotypic profile in patients with OSAH. METHODS: After obtaining diagnostic polygraphy from a group of consecutive patients with OSAH, we performed the dial-down CPAP technique during nocturnal polysomnography and used it as reference method. This allowed assessment of upper airway collapsibility, loop gain (LG), arousal threshold (AT), and upper airway muscle gain (UAG). We compared these results with a daytime protocol based on negative expiratory pressure (NEP) technique for evaluating upper airway collapsibility and UAG, on maximal voluntary apnea for LG, and on clinical predictors for AT. RESULTS: Of 15 patients studied, 13 patients with OSAH accurately completed the two procedures. There were strong (all r2 > 0.75) and significant (all p < 0.001) correlations for each phenotypic trait between the measurements obtained through the reference method and those achieved during wakefulness. CONCLUSION: It is possible to phenotype patients with OSAH from a pathophysiological point of view while they are awake. Using this approach, cutoff values corresponding to those usually adopted using the reference method can be identified to detect abnormal traits, achieving profiles similar to those obtained through the dial-down CPAP technique.

Exercise tolerance in obstructive sleep apnea-hypopnea (OSAH), before and after CPAP treatment: Effects of autonomic dysfunction improvement.

BACKGROUND: Obstructive sleep apnea hypopnea (OSAH) is associated with decreased exercise tolerance and autonomic abnormalities and represents a risk for cardiovascular diseases. The aim of the study was to evaluate the effects of CPAP on cardiovascular autonomic abnormalities and exercise performance in patients with OSAH without changes in lifestyle and body weight during treatment. METHODS: Twelve overweight subjects with OSAH underwent anthropometric measures, autonomic cardiovascular and incremental symptom-limited cardio-respiratory exercise tests before and after two months of treatment with CPAP. RESULTS: Lower frequency component of power spectrum of heart rate variability (59.5±24.2 msec2 vs 43.2±25.9 msec2; p<0.05) and improvements of maximal workload (99.3±13.5 vs 108.3±16.8%pred.; p<0.05) and peak oxygen consumption (95.3±7.6 vs 105.5±7.9%pred.; p<0.05) were observed in these patients after CPAP, being their BMI unchanged. CONCLUSIONS: CPAP-induced decrease of sympathetic hyperactivity is associated with better tolerance to the effort in OSAH patients that did not change their BMI and lifestyle, suggesting that OSAH limits per se the exercise capacity.

Hyperventilation and seizures in an adolescent female.

A 16 year-old girl was admitted after suffering from recurrent episodes of dyspnea and stridor, cyanosis, loss of contact, stiffening of all four limbs, clenching of the jaw and eye retroversion that lasted for a few seconds to a minute, followed by slow recovery of consciousness without any loss of sphincter control. These symptoms began at the age of 11 and worsened over time. Prolonged rate corrected QT intervals was observed with an ECG. Two cardio-respiratory monitorings were performed (one during daytime hours while the patient was awake, and one at night time while the patient slept). Daytime recordings showed 17 central apnoeas and 97 central hypopneas, with an apnea-hypopnea index (AHI) of 13.2 events/hour, that were associated with severe oxyhemoglobin desaturation. In contrast, night time recordings were normal (AHI=1.1 events/hour). The patient underwent diurnal monitoring of transcutaneous pCO2(PtcCO2), transcutaneous O2(PtcO2), SpO2 and end tidal CO2 (PETCO2), with simultaneous monitoring of regional cerebral oxymetry (rSO2) which showed values of PtcCO2 between 8 and 15 mmHg, suggesting several episodes of marked hyperventilation. Twenty-nine episodes of severe arterial desaturation (SpO2<50%) were registered, all after the same number of apnea events, with ascent of PtcO2 up to 28 mmHg at the end of apnea. During the final phase of apnea, the patient showed cyanosis, contact disturbance, grimaces, oral movements of rhyme, and, on three occasions, partial seizures. A mask was packaged and applied daytime to the face of the patient during episodes of hyperventilation to prevent, together with a psychiatric follow up, rapid falls of PaCO2 levels determining central apnoeas.

Dynamic pulmonary hyperinflation and low grade systemic inflammation in stable COPD patients.

BACKGROUND AND OBJECTIVES: It is increasingly recognized that a low grade of systemic inflammation occurs in patients with advanced chronic obstructive pulmonary disease (COPD). C-reactive protein (CRP), a marker of systemic chronic inflammatory response, has been related with decreased survival in large cohorts of COPD patients. The aim of the study was to assess if resting dynamic pulmonary hyperinflation (DH) is linked to the presence of systemic inflammation in COPD. MATERIALS AND METHODS: In a 12-month retrospective study involving 55 out-patients with COPD (FEV1 59+/- 23% pred.) examined in stable conditions, inspiratory capacity (IC) was measured at rest and considered as index of DH when lower than 80% predicted. Simultaneously, CRP (by immuno-turbidometry) and white blood cells (WBC), uric acid and alpha-1 globulins were measured in the venous blood in the morning before eating. RESULTS: CRP was significantly increased in the COPD patients with IC < 80% pred. (n = 35; IC = 61 + 14% pred.) as compared with that measured in COPD patients with IC > 80% pred. (n = 20; IC = 97 + 13% pred.), amounting to 0.70 +/- 0.59 vs 0.29 +/- 0.28 mg/dl, respectively (p < 0.01). CRP was inversely related to IC (% pred.) (r = 0.45, p < 0.01). WBC, serum uric acid (an endogenous danger signal), and albumin and alfa-1 globulins were not different between the two groups. DISCUSSION: These results show that the IC reduction is associated with higher serum levels of CRP in stable COPD patients, suggesting a potential role of dynamic pulmonary hyperinflation on development and maintenance of low grade systemic inflammation in COPD.

Inspiratory capacity predicts mortality in patients with chronic obstructive pulmonary disease.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) severity is usually graded upon the FEV(1) reduction and FEV(1) has been considered the most important mortality predictor with age in COPD. Recent studies suggest other factors as more powerfully related to mortality than FEV(1) in COPD patients. AIM: To assess the impact of inspiratory capacity (IC) on mortality and morbidity in COPD patients during a 5-year follow-up period. METHODS: We recruited 222 patients with mild-to-moderate COPD from January 1995 to December 2001 with an average follow-up period of 60 months (range 30-114 months). Among different respiratory parameters measured in stable conditions FEV(1), FEV(1)/FVC%, IC and PaO(2), PaCO(2) and BMI were chosen and their relationships with all-cause and respiratory mortality and with morbidity were assessed. RESULTS: All these variables were associated with mortality at the univariate analysis. However, in a multivariate regression analysis (Cox proportional hazards model) for all-cause mortality age (year), IC (%pred.) and PaO(2) (mmHg) remained the only significant, independent predictors (HR=1.056, 95%CI: 1.023-1.091; HR=0.981, 95%CI: 0.965-0.998; HR=0.948, 95%CI: 0.919-0.979, respectively). According to the same analysis, IC (%pred.) and PaO(2) (mmHg) were significant independent predictors for respiratory mortality (HR=0.967, 95%CI: 0.938-0.997; HR=0.919, 95%CI: 0.873-0.969) together with FEV(1)/FVC% and BMI (kg/m(2)) (HR=0.967, 95%CI: 0.933-1.022; HR=0.891, 95%CI: 0.807-0.985, respectively). IC (%pred.), FEV(1)/FVC%, and PaO(2) (mmHg) were also significantly related to morbidity, as independent predictors of hospital admissions because of exacerbations (OR=0.980, 95%CI: 0.974-0.992; OR=0.943, 95%CI: 0.922-0.987; OR=0.971, 95%CI: 0.954-0.996, respectively). CONCLUSION: IC (%pred.) is a powerful functional predictor of all-cause and respiratory mortality and of exacerbation-related hospital admissions in COPD patients.

Skin prick-test reactivity to aeroallergens and allergic symptoms in an urban population of central Italy: a longitudinal study.

BACKGROUND: Cross-sectional studies report an increasing prevalence of allergic diseases, such as rhinitis and asthma. Not thoroughly known, instead, is the natural history of allergic sensitization and the progress of the allergic disease-related symptoms. AIM: The purpose of this study was to evaluate longitudinally the skin reactivity for the most common aeroallergens and the allergic symptoms in an urban population living in Perugia, a town of central Italy with a low-level of air pollution exposure. METHODS: In the 1998-1999 period 788 subjects were tested for skin reactivity to a panel of aeroallergens and underwent the administration of a questionnaire. These same subjects were part of a cohort of 1200 subjects who participated in a previous epidemiological study performed in 1984-1985 using the same tools. Subjects were aged between 14 and 64 years at the time of the first survey. RESULTS: In the present survey 196 subjects (24.9%) had skin reactivity to at least one aeroallergen, while in the previous survey 143 subjects (18.1%) had skin prick-test reactivity. The increase of the skin reactivity between the two observations was highly significant (P<0.001) and was mainly observed in subjects <40-years old. The greatest increment in skin reactivity was seen to Dermatophagoides pteronyssinus (house dust mite) allergen. Data obtained from questionnaires showed that subjects who declared allergic symptoms increased from 341 (43.3%) to 380 (48.2%). However, the increase was significant (P<0.01) only in subjects who had a positive association between allergic symptoms and prick-test reactivity and was greater for rhino-conjunctivitis than for asthma-related symptoms. CONCLUSIONS: In a cohort of urban population of the centre of Italy, exposed to a low and stable level of air pollution, the sensitization to common aeroallergens increased with time, mostly in people <40-years of age. The greatest increment was found for indoor allergens such as Dermatophagoides pteronysimus. A significant increase in allergic symptoms, mainly related to rhino-conjunctivitis, was observed only in the presence of positive prick test.

Upper airway dynamics during negative expiratory pressure in apneic and non-apneic awake snorers.

BACKGROUND: The ability of negative expiratory pressure (NEP) technique to differentiate between awake snorers with and without obstructive sleep apnea-hypopnea (OSAH) was investigated. METHODS: Forty-eight subjects with sleep disordered breathing (SDB) and 7 healthy subjects, as non-snorer controls, underwent the NEP application of -5 and -7 cmH2O in the seated and supine position during wakefulness, after performing a sleep study. The upper airway collapsibility was assessed by computing the volume exhaled during the first 0.5 sec. (V,NEP0.5) and 1 sec. (V,NEP1) following the NEP start. RESULTS: Patients with severe (AHI > or = 30) (n = 19) and mild-to-moderate (AHI <30 and >5) (n = 15) OSAH had lower V,NEP0.5 (340 +/- 88 ml) as compared to snorers (AHI < or = 5) (n = 14) (427 +/- 101 ml; p < 0.01) and controls (n = 7) (492 +/- 69 ml; p < 0.001) in the supine position with NEP -5 cmH2O. Less significant differences among the different groups were observed for V,NEP0.5 in the seated position with NEP -5 cmH2O and in both positions with NEP -7 cmH2O (only OSAH patients vs controls, p < 0.001). Similar results were obtained for V,NEP1 in either position by using both NEP -5 cmH2O and -7 cmH2O. In spite of this, a substantial overlapping of V,NEP0.5 and V,NEP1 between snorers and OSAH patients did not allow to identify a reliable diagnostic cut-off level. An inverse correlation with AHI was found for V,NEP0.5 in the supine position with NEP -5 cmH2O (rs = -0.46, p < 0.05) in severe OSAH patients. CONCLUSION: The awake OSAH patients exhibit values of V,NEP0.5 and V,NEP1 lesser than those of awake snorers. The NEP technique, however, appears to have a limited usefulness as clinical tool for routine screening of the OSAH patients during wakefulness.

Reference values and repeatability of inspiratory capacity for men and women aged 65-85.

The inspiratory capacity (IC) has recently gained importance because it may signal the occurrence of dynamic hyperinflation at rest or during exercise by reflecting changes in the end expiratory lung volume (EELV). However, reliable predicted values for IC are not currently available. The aim of the study was to generate predictive equations for reference values of IC in adults aged 65-85 living in Italy and to determine its limits of the within test-session repeatability. From the control group (n=429) of the SARA study data base, 241 (161 females) never smoked, non-obese (BMI<30 kg/m2) healthy subjects aged 65-85 who were able to correctly perform at least two manoeuvres of IC were selected. A model that incorporated age, height and body mass index as significant predictors in either sexes produced predicting equations for IC with a coefficient of determination of r2=.36 and .34 for females and males, respectively. Ninety per cent of all the subjects were able to keep the second highest IC within 200 ml (<9%) from the best IC. No significant gender difference was found for IC repeatability. We provided the equations for deriving reliable IC reference values that can be applied in the elderly people living in southern Europe. In this population IC showed limits of the within-session repeatability similar to those accepted for other spirometric indices such as FEV1 and FVC.

Neutrophilic inflammation and IL-8 levels in induced sputum of alpha-1-antitrypsin PiMZ subjects.

BACKGROUND: Severe alpha-1-antitrypsin deficiency (AATD), due to homozygosity for the protease inhibitor (Pi) Z allele, is a genetic risk factor for chronic obstructive pulmonary disease (COPD). In a previous study the sputum of severe AATD subjects with airflow obstruction showed a pattern of cellular inflammation similar to COPD patients. It is uncertain whether heterozygotes for the Z allele or intermediate deficiency (PiMZ) have an increased risk of developing COPD. METHODS: Sputum cell counts and the supernatant level of the neutrophil chemoattractant interleukin (IL)-8 were investigated by sputum induction in 10 non-smoker asymptomatic PiMZ subjects with normal pulmonary function, 10 patients with stable COPD, and 10 age matched normal subjects. Data are expressed as mean (SD). RESULTS: The mean (SD) number of neutrophils was significantly higher (p<0.01) in the sputum of PiMZ subjects (84.5 (22.2) x10(4)/ml) and patients with COPD (126.9 (18.8) x10(4)/ml) than in matched normal subjects (55.0 (8.7) x10(4)/ml). IL-8 levels were increased in PiMZ subjects (828.5 (490.6) ng/ml; median 1003.0 ng/ml; range 1260-100 ng/ml) and in COPD patients (882.5 (524.3) ng/ml; median 934.9 ng/ml; range 1506-258 mg/ml) compared with normal subjects (3.5 (0.5) ng/ml; median 3.5 ng/ml; range 4.5-2.5 ng/ml). There was a significant positive correlation between IL-8 supernatant concentration and neutrophil count in PiMZ subjects (p = 0.036; r = 0.66). An inverse correlation was observed between the percentage of neutrophils and forced expiratory volume in 1 second (% predicted) in patients with COPD (p = 0.04; r = -0.43). CONCLUSIONS: These findings indicate that PiMZ subjects without airflow obstruction may have an IL-8 related neutrophilic inflammation in the airways, similar to stable COPD patients, suggesting an increased risk of developing pulmonary changes.

Unaltered respiratory-related evoked potentials after acute diaphragm dysfunction in humans.

Respiratory muscles play an important role in the origin of respiratory sensations. Data dissecting the role of the diaphragm and other inspiratory muscles are scarce. This study aimed to determine the impact of diaphragm dysfunction following inspiratory resistive loading on respiratory-related evoked potentials considered as a neurophysiological substrate of certain types of respiratory sensations. Altogether, nine subjects aged 25-50 yrs (six females) participated in the study. Transdiaphragmatic pressure output of cervical magnetic stimulation (with subdivision in oesophageal and gastric component), and respiratory-related evoked potentials (C3 and C4 derivations in the international 10-20 system) following mid-inspiratory occlusions were studied before and after an inspiratory-resistive loading challenge. Predominant diaphragm dysfunction was observed in seven subjects (average 28% reduction in transdiaphragmatic pressure, from 27.25-19.91 cmH2O, with increased oesophageal-to-gastric pressure ratio). The latencies and amplitudes of all the components of the respiratory-related evoked potentials were unchanged. The study concluded that predominant diaphragm fatigue does not affect respiratory-related evoked potentials.

Sleep-disordered breathing in nonobese diabetic subjects with autonomic neuropathy.

To assess the occurrence and nature of sleep-disordered breathing (SDB) in 26 adult, nonobese diabetics (18 with autonomic neuropathy (DAN+) (age 45 (41-50) yrs; body mass index (BMI) 24.1 (22-26) kg x m(-2)) and eight without autonomic neuropathy (DAN-) (age 45 (35-55) yrs; BMI 24.8 (23-26) kg x m(-2))) overnight full sleep studies and measurements of central and peripheral carbon dioxide (CO2) chemosensitivity were performed. DAN+ were divided in two subgroups, according to the presence (DAN+PH+; n=10) or absence (DAN+PH-; n=8) of postural hypotension. Ten normal subjects were studied as controls (age 42 (36-48) yrs; BMI 24.4 (23-25) kg x m(-2)). In contrast to DAN- and controls, who did not show SDB, five DAN+ (four DAN+PH- and one DAN+PH+) had an apnoea/hypopnoea index > or = 10 and four DAN+ (two DAN+PH- and two DAN+PH+) had an apnoea index > or = 5. All the events were obstructive, occurring mainly during rapid eye movement (REM) sleep. Ten DAN+ exhibited a mean lowest oxygen saturation < 90% during REM sleep. No periodic breathing or central sleep apnoeas were found in DAN+PH+, although they had an enhanced central chemoresponsiveness to CO2. Both DAN+ subgroups showed a marked reduction in peripheral CO2 chemosensitivity. In conclusion, adult nonobese diabetics with autonomic neuropathy, independent of the severity of their dysautonomy, have obstructive sleep apnoea/hypopnoea with a frequency > 30%. A decrease in peripheral carbon dioxide chemosensitivity prevents adult nonobese diabetics with autonomic neuropathy and postural hypotension from experiencing posthyperventilatory central sleep apnoea, despite an increased hypercapnic central drive.

Airway hyperresponsiveness in a large group of subjects with alpha1-antitrypsin deficiency: a cross-sectional controlled study.

BACKGROUND: It has been suggested that subjects with alpha-antitrypsin (AAT) deficiency, lacking a major antiprotease defence against airway inflammation, might be more susceptible of development of airway hyperresponsiveness (AHR). Moreover, lower AAT blood levels might also be able to influence the severity of AHR. OBJECTIVES: This study was aimed to investigate the prevalence of AHR in a large group of subjects with AAT deficiency included in the Italian Registry and to evaluate the relationship between AAT blood levels and the severity of AHR in this population. DESIGN: Cross-sectional controlled study. SETTING: Regional Reference Centre for AAT deficiency in Brescia, Italy. METHODS: A total of 114 subjects with AAT deficiency underwent pulmonary function tests. Eighty-six were eligible to perform a bronchial provocation test with methacholine (MCh) (baseline FEV1 > 60% predicted) to assess the provocative dose producing a 20% fall of FEV1 (PD20FEV1). Similar measurements were performed in a control group of 27 age-matched normal subjects. RESULTS: The prevalence of AHR (PD20FEV1 < 2000 microg MCh) was not different between AAT deficiency subjects and controls (16.3% and 11.1%, respectively; P = 0.66), and also amongst two subgroups of AAT deficiency subjects divided according to different protease inhibitor (Pi) phenotypes (PiMZ-MS, PiSZ-ZZ). Hyperresponsive subjects with AAT deficiency, however, showed a positive correlation between AAT blood levels and PD20FEV1 values (r = 0.71, P < 0.01). CONCLUSIONS: These findings indicate that AAT deficiency subjects did not exhibit a greater prevalence of airway hyperresponsiveness as compared with control subjects, but suggest that, in the subset of AAT deficiency subjects hyperresponsive to MCh, lower levels of AAT are associated with a higher severity of AHR.

Volume effect and exertional dyspnoea after bronchodilator in patients with COPD with and without expiratory flow limitation at rest.

BACKGROUND: A study was undertaken to investigate whether bronchodilators are associated with less breathlessness at rest and during light exercise in patients with moderate to severe chronic obstructive pulmonary disease (COPD) with resting tidal expiratory flow limitation (EFL; flow limited (FL)) compared with those without EFL (non-flow limited (NFL)). METHODS: Twenty subjects (13 men) of mean (SD) age 65 (8) years (range 43-77) suffering from COPD with forced expiratory volume in 1 second (FEV(1)) 47 (18)% predicted were studied before and after inhalation of salbutamol (400 microg). Routine pulmonary function tests were performed in the seated position at rest. EFL was assessed by the negative expiratory pressure (NEP) method and changes in end expiratory lung volume (EELV) were inferred from variations in inspiratory capacity (IC). Dyspnoea was measured using the Borg scale at rest and at the end of a 6 minute steady state exercise test at 33% of the maximal predicted workload. RESULTS: EFL occurred in 11 patients. Following salbutamol IC did not change in NFL patients but increased by 24% (95% CI 15 to 33) in FL patients (p<0.001). Maximal inspiratory pressure (PImax) improved at EELV from 45 (95% CI 26 to 63) to 55 (95% CI 31 to 79) cm H(2)O (p<0.05) in FL patients after salbutamol but remained unchanged in NFL patients. The workload performed during exercise amounted to 34 (95% CI 27 to 41) and 31 (95% CI 21 to 40) watts (NS) for patients without and with EFL, respectively. After salbutamol, dyspnoea did not change either at rest or during exercise in the NFL patients, but decreased from 0.3 (95% CI -0.1 to 0.8) to 0.1 (95% CI -0.1 to 0.4) at rest (NS) and from 3.7 (95% CI 1.7 to 5.7) to 2.6 (95% CI 1.1 to 4.0) at the end of exercise (p<0.01) in FL patients. CONCLUSIONS: Patients with COPD with EFL may experience less breathlessness after a bronchodilator, at least during light exercise, than those without EFL. This beneficial effect, which is closely related to an increase in IC at rest, occurs even in the absence of a significant improvement in FEV(1) and is associated with a greater PImax.

Expiratory flow limitation and orthopnea in massively obese subjects.

BACKGROUND: Morbidly obese subjects, who often complain about breathlessness when lying down, breathe at low lung volume with a reduced expiratory reserve volume (ERV). Therefore, during tidal breathing the expiratory flow reserve is decreased, promoting expiratory flow limitation (EFL), which is more likely to occur in the supine position, when the relaxation volume of the respiratory system, and hence the functional residual capacity (FRC), decrease because of the gravitational effect of the abdominal contents. PURPOSE: The aim of the study was to assess EFL and orthopnea in massively obese subjects and to evaluate whether orthopnea was associated with the development of supine EFL. METHODS: In 46 healthy obese subjects (18 men) with a mean (+/- SD) age of 44 +/- 11 years and a mean body mass index (BMI) of 51 +/- 9 kg/m(2), we assessed EFL in both the seated and the supine positions by the negative expiratory pressure method and assessed postural changes in FRC by measuring the variations in the inspiratory capacity (IC) with recumbency. Simultaneously, dyspnea was evaluated in either position using the Borg scale dyspnea index (BSDI) to determine the presence of orthopnea, which was defined as any increase of the BSDI in the supine position. RESULTS: Partial EFL was detected in 22% and 59%, respectively, of the overall population in seated and supine position. The mean increase in the supine IC amounted to 120 +/- 200 mL (4.1 +/- 6.4%), indicating a limited decrease in FRC with recumbency in these subjects. Orthopnea, although mild (mean BSDI, 1.7 +/- 1.3), was claimed by 20 subjects, and in 15 of them EFL occurred or worsened in the supine position. Orthopnea was associated with lower values of seated ERV (p < 0.05) and was marginally related to supine EFL values (p = 0.07). No significant effect of age, BMI, obstructive sleep apnea-hypopnea syndrome, FEV(1), and forced expiratory flow at 75% of vital capacity was found on either orthopnea or EFL. CONCLUSION: In morbidly obese subjects, EFL and dyspnea frequently occur with the subject in the supine position, and both supine EFL and low-seated ERV values are related to orthopnea, suggesting that dynamic pulmonary hyperinflation and intrinsic positive end-expiratory pressure may be partly responsible for orthopnea in massively obese subjects.

[Hospital discharge report of patients with chronic obstructive pulmonary disease]. / La relazione di dimissione ospedaliera del paziente con broncopneumopatia cronica ostruttiva.

Chronic obstructive pulmonary disease usually doesn't require hospital admission. However, the course of the disease is characterized by frequent exacerbations that often require hospital admission, representing a good chance to define all aspects of chronic obstructive pulmonary disease and improve the management of the patient. When the patient is discharged from the hospital, an essential Report should specify the reasons of admission, the symptoms (e.g.: cough, sputum production and dyspnoea) and the findings of physical examination, the results of the main laboratory and radiological tests performed (pulmonary function tests are essential to define the severity of degree of airway obstruction and useful for its longitudinal assessment), the treatment administered, the final diagnosis, the suggested therapy, the follow-up appointments and the recommendations (nutrition, psychological support, muscle reconditioning) of a possible rehabilitation program.

Cerebrovascular reactivity and hypercapnic respiratory drive in diabetic autonomic neuropathy.

Because abnormalities in cerebrovascular reactivity (CVR) in subjects with long-term diabetes could partly be ascribed to autonomic neuropathy and related to central chemosensitivity, CVR and the respiratory drive output during progressive hypercapnia were studied in 15 diabetic patients without (DAN-) and 30 with autonomic neuropathy (DAN+), of whom 15 had postural hypotension (PH) (DAN+PH+) and 15 did not (DAN+PH-), and in 15 control (C) subjects. During CO(2) rebreathing, changes in occlusion pressure and minute ventilation were assessed, and seven subjects in each group had simultaneous measurements of the middle cerebral artery mean blood velocity (MCAV) by transcranial Doppler. The respiratory output to CO(2) was greater in DAN+PH+ than in DAN+PH- and DAN- (P < 0.01), whereas a reduced chemosensitivity was found in DAN+PH- (P < 0.05 vs. C). MCAV increased linearly with the end-tidal PCO(2) (PET(CO(2))) in DAN+PH- but less than in C and DAN- (P < 0.01). In contrast, DAN+PH+ showed an exponential increment in MCAV with PET(CO(2)) mainly >55 Torr. Thus CVR was lower in DAN+ than in C at PET(CO(2)) <55 Torr (P < 0.01), whereas it was greater in DAN+PH+ than in DAN+PH- (P < 0.01) and DAN- (P < 0.05) at PET(CO(2)) >55 Torr. CVR and occlusion pressure during hypercapnia were correlated only in DAN+ (r = 0.91, P < 0.001). We conclude that, in diabetic patients with autonomic neuropathy, CVR to CO(2) is reduced or increased according to the severity of dysautonomy and intensity of stimulus and appears to modulate the hypercapnic respiratory drive.

[Alpha 1-antitrypsin deficiency: the Brescia clinical study]. / Il deficit di alpha 1-antitripsina: lo studio clinico di Brescia.

In a longitudinal clinical study, two hundred subjects have been evaluated in order to identify alpha 1-antitrypsin deficiency patients. According to their serum alpha 1-antitrypsin levels, they have been divided into three groups: 25 patients with severe deficiency (with both pathological alleles--ZZ, SZ or Z and rare deficiency allele--and, if clinically suggested, to be treated with augmentation therapy), 92 patients with intermediate deficiency (with one pathological allele, to be followed up in order to evaluate the risk to develop deficiency related disease) and 63 healthy subjects (normal alleles MM). They performed lung function test (including cardiopulmonary exercise test and methacholine bronchial challenge) chest X-ray and high resolution computed tomography, blood tests. Severe deficiency patients also performed perfusional lung scan to detect early disorders of blood flow, evaluation of arterial blood gases and liver echotomography. Expiratory flow limitation, the prevalence of vascular disease, the amount of urine elastin products and correlations between the amount of nitric oxide exhaled and bronchial hyperresponsiveness have been also investigated. The study showed that in Brescia county the deficiency is more common than expected and that evaluation of liver and vessels might be as useful as lung function tests. In addition, beneficial effect on local system has been observed. The longitudinal study might permit to detect early organ damage and to eliminate additive risk factors.

Impairment of the respiratory system in diabetic autonomic neuropathy.

Diabetic autonomic neuropathy (DAN) may affect up to 30% of the diabetic population. Sometimes DAN becomes clinically manifest causing specific symptoms and signs; more often, however, DAN is responsible for subtle alterations detectable only by functional tests, as in the case of the respiratory system. At first, abnormalities both in the bronchomotor tone and aspecific airway responsiveness to different stimuli were recognised in diabetic patients with DAN, indicating a defective control of mechanisms which regulate the bronchial calibre in these subjects. Subsequently, peculiar changes in breathing pattern and greater ventilatory requirements have been observed during incremental exercise in diabetics with DAN, suggesting an altered control of breathing in stressful conditions. Alterations in either peripheral or central chemosensitivity have been repeatedly shown in these patients, with marked differences related to the severity of DAN, concerning the neuro-muscular and ventilatory responsiveness to CO2. Following anecdotal reports, respiratory disturbances during sleep have been more carefully investigated in diabetic subjects and greater prevalence of sleep apnea, mainly in the obstructive form, has been found in the presence of DAN. The underlying mechanisms of sleep disordered breathing, however, are poorly understood in DAN and further studies are needed to elucidate them.

Expiratory flow limitation as a determinant of orthopnea in acute left heart failure.

OBJECTIVES: To assess the contribution of expiratory flow limitation (FL) in orthopnea during acute left heart failure (LHF). BACKGROUND: Orthopnea is typical of acute LHF, but its mechanisms are not completely understood. In other settings, such as chronic obstructive pulmonary disease, dyspnea correlates best with expiratory FL and can, therefore, be interpreted as, in part, the result of a hyperinflation-related increased load to the inspiratory muscles. As airway obstruction is common in acute LHF, postural FL could contribute to orthopnea. METHODS: Flow limitation was assessed during quiet breathing by applying a negative pressure at the mouth throughout tidal expiration (negative expiratory pressure [NEP]). Flow limitation was assumed when expiratory flow did not increase during NEP. Twelve patients with acute LHF aged 40-98 years were studied seated and supine and compared with 10 age-matched healthy subjects. RESULTS: Compared with controls, patients had rapid shallow breathing with slightly increased minute ventilation and mean inspiratory flow. Breathing pattern was not influenced by posture. Flow limitation was observed in four patients when seated and in nine patients when supine. In seven cases, FL was induced or aggravated by the supine position. This coincided with orthopnea in six cases. Only one out of the five patients without orthopnea had posture dependent FL. Control subjects did not exhibit FL in either position. CONCLUSIONS: Expiratory FL appears to be common in patients with acute LHF, particularly so when orthopnea is present. Its postural aggravation could contribute to LHF-related orthopnea.

Flow limitation: an overview.

Expiratory flow limitation (EFL) refers to a functional condition in which expiratory flow cannot increase and, hence, is maximal under the prevailing conditions. Many factors, alone or combined, may cause EFL. Among them, airway obstruction, expiratory flow rate and body posture are the most important. EFL normally occurs during the forced expiratory manoeuvre after peak expiratory flow. However, its presence during tidal breathing either throughout exercise or at rest, initially in the supine and then in the seated position, is an abnormal finding which reflects progressively greater mechanical impairment. EFL promotes dynamic pulmonary hyperinflation (DH) by prolonging the time required for the respiratory system to reach its relaxation volume during expiration. Moreover, in the presence of EFL, any increase in expiratory flow can be accomplished only by raising the end-expiratory lung volume allowing tidal breathing to occur at a higher absolute lung volume. This mechanism, however, besides being physically limited, leads to an increment in DH and intrinsic end-expiratory alveolar pressure, adding an increasing threshold load on the inspiratory muscles, which become functionally weaker, and eliciting dyspnoea. In advanced chronic obstructive pulmonary disease, bronchodilators and lung volume reduction surgery do not usually reverse expiratory flow limitation, but they appear to be useful because they often allow expiratory flow limitation to occur at a lower absolute lung volume, thus reducing dynamic pulmonary hyperinflation and limiting exertional dyspnoea.