Claudio Tantucci

Effect of salbutamol on dynamic hyperinflation in chronic obstructive pulmonary disease patients

Expiratory flow limitation (EFL), which promotes dynamic hyperinflation and increased work of breathing, often occurs in chronic obstructive pulmonary disease (COPD). The purpose of this study was to assess the effect of bronchodilators on EFL and end-expiratory lung volume in patients with moderate-to-severe COPD. EFL was assessed by applying negative expiratory pressure (NEP) at the mouth during tidal expiration. EFL was present when expiratory flow did not increase or increased only in the early phase of expiration with NEP. In 18 patients (age 65+/-2 yrs; forced expiratory volume in one second (FEV1)=45+/-4% predicted) pulmonary function tests and a series of NEP (-3.5 cmH2O) test breaths were performed at rest in a sitting position before and 20 min after inhalation of 400 microg of salbutamol. EFL was detected in 11 patients and persisted after salbutamol in all of these flow-limited (FL) patients. After bronchodilator administration FL patients exhibited a significant decrease in functional residual capacity (FRC) associated with an increase in inspiratory capacity (IC). In contrast, no changes in FRC and IC were observed in the seven non flow-limited (NFL) patients after administration of salbutamol. Except for one NFL patient, the other 17 patients (six NFL and 11 FL) had no reversibility of their bronchial obstruction (delta FEV1 <10% pred). In conclusion, patients with chronic obstructive pulmonary disease and expiratory flow limitation, even if nonresponders in terms of forced expiratory volume in one second, may benefit from bronchodilators because they can breathe, still in a flow-limited manner, at a lower lung volume.

Reference values for exhaled nitric oxide (reveno) study.

BackgroundDespite the widespread use of fractional exhaled nitric oxide (FENO) as a biomarker of airways inflammation, there are no published papers describing normal FENO values in a large group of healthy adults.ObjectiveThe aim of this study was to establish adult FENO reference values according to the international guidelines.MethodsFENO was measured in 204 healthy, non-smoking adults with normal spirometry values using the on-line single-breath technique, and the results were analysed chemiluminescently.ResultsThe main result of the study was the significant difference in FENO values between men and women, thus indicating that gender-based reference FENO values are necessary. The FENO levels obtained at expiratory flows of 50 ml/s ranged from 2.6 to 28.8 ppb in men, and from 1.6 to 21.5 ppb in women.ConclusionWe propose reference FENO values for healthy adult men and women that could be used for clinical and research purposes.

Lung function decline in COPD

The landmark study of Fletcher and Peto on the natural history of tobacco smoke-related chronic airflow obstruction suggested that decline in the forced expiratory volume in the first second (FEV1) in chronic obstructive pulmonary disease (COPD) is slow at the beginning, becoming faster with more advanced disease. The present authors reviewed spirometric data of COPD patients included in the placebo arms of recent clinical trials to assess the lung function decline of each stage, defined according to the severity of airflow obstruction as proposed by the Global Initiative for Chronic Obstructive Lung Disease (GOLD) guidelines. In large COPD populations the mean rate of FEV1 decline in GOLD stages II and III is between 47 and 79 mL/year and 56 and 59 mL/year, respectively, and lower than 35 mL/year in GOLD stage IV. Few data on FEV1 decline are available for GOLD stage I. Hence, the loss of lung function, assessed as expiratory airflow reduction, seems more accelerated and therefore more relevant in the initial phases of COPD. To have an impact on the natural history of COPD, it is logical to look at the effects of treatment in the earlier stages.

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.

Usefulness of Exhaled Nitric Oxide and Sputum Eosinophils in the Long-term Control of Eosinophilic Asthma

BACKGROUND The aim of the present study was to treat unstable asthma according to exhaled nitric oxide (eNO) and induced-sputum eosinophils (sEos) levels to assess if this strategy is better than the conventional approach based on symptoms and function to achieve asthma control. METHODS Fourteen patients with mild-to-moderate persistent asthma (6 men, 8 women) were recruited. During the recruitment visit, the patients, previously treated for asthma following Global Initiative for Asthma recommendations, underwent clinical evaluation and pulmonary function tests (PFTs). Then, after 4 weeks of washout from inhaled antiinflammatory treatment, the patients underwent a basal visit performing PFTs, challenge test to methacholine, and determination of eNO and sEos counts. These procedures were repeated after 3, 6, and 12 months while the patients were treated with inhaled steroids in a stepwise fashion according to eNO and sEos values. RESULTS At the end of the study, a significant decrease in eNO and sEos was observed (57.2 +/- 32.8 parts per billion [ppb] vs 22.1 +/- 10.8 ppb, p < 0.01; and 27.1 +/- 27.1% vs 3.7 +/- 3.5%, p < 0.01, respectively). A close correlation (r2 = 0.41, p < 0.01) between the percentage change of eNO and sEos was observed only after 6 months. Patients treated according to the levels of these inflammatory markers had fewer symptoms and fewer exacerbations compared to those the year before when they were conventionally treated. CONCLUSIONS Our results show the usefulness of eNO and sEos for titrating treatment in asthmatic patients in order to achieve better long-term control of the disease. The eNO decrease reflects adequately the reduction of sEos only after 6 months.

Autonomic Neuropathy Increases the Risk of Obstructive Sleep Apnea in Obese Diabetics

Background: Nonobese diabetics with diabetic autonomic neuropathy (DAN) show an elevated prevalence of obstructive sleep apnea-hypopnea (OSAH). Objective: It was the aim of this study to assess if the presence of DAN could further increase the risk of developing OSAH in obese diabetics. Methods: Eighteen obese diabetic patients, 8 with DAN [age 57 ± 5 years, body mass index (BMI) 35 ± 4] and 10 without DAN (age 56 ± 8 years, BMI 37 ± 5), were recruited. Ten age-matched obese subjects were studied as controls (age 53 ± 12 years, BMI 34 ± 3). All subjects underwent a cardiorespiratory sleep study in the in-hospital sleep laboratory to obtain the apnea-hypopnea index (AHI) and oxygen desaturation indices. Results: Diabetics with DAN (Ob-DAN+) had a higher AHI than diabetics without DAN (Ob-DAN–) and controls, amounting to 39.5 ± 13 versus 15.8 ± 12 (p < 0.01) and 19.3 ± 21 (p < 0.05), respectively. A moderate-to-severe OSAH (AHI ≧15) occurred in all Ob-DAN+ and only in 4 Ob-DAN– and 4 control patients. Moreover, the indices reflecting the impairment of oxygen saturation (SaO2) during sleep such as the mean lowest SaO2 and sleep time with a SaO2 <90% were more severely affected in Ob-DAN+ patients compared with the other groups and were associated with longer obstructive respiratory events. Conclusions: Apneas-hypopneas are more frequent and last longer in Ob-DAN+ than in other obese subjects, with or without diabetes.

Energy cost of exercise in multiple sclerosis patients with low degree of disability

In 10 patients (five females) suffering from multiple sclerosis with mild degree of disability, (EDSS ranging from 0 to 2) and in 10 age and sex matched control subjects we investigated lung function, respiratory muscles strength and cardiorespiratory response to incremental exercise in order to assess the metabolic cost of exercise. In the absence of any impairment of lung volumes and flows and in-and expiratory maximal mouth pressures, at peak of exercise oxygen consumption (VO2max=1886 ± 145 ml/min) and workload (Wmax = 137 ± 9.8 watts) were slightly diminished in patients, as compared with controls (VO2max = 2246 ± 196 ml/min and Wmax = 164 ± 14.7 watts). These findings were associated with an increased heart rate (HR) and reduced oxygen pulse (VO2/HR) at the same workloads. During the whole exercise, however, the slope of the linear relationship between VO2 and work exhibited by the patients, amounting to 9.9 ± 0.6 ml/min/watt, was similar to that of the controls (10.9 ± 0.42 ml/min/watt). Incidentally, both at rest and during exercise, the patients showed a significantly greater minute ventilation (due to a faster respiratory rate, associated with an augmented dead space (P<0.05). We conclude that an increase of metabolic cost of exercise does not occur in multiple sclerosis patients with mild disability, suggesting a lack or a low degree of spasticity and/or ataxia elicited by the effort Thus, their exertional capacity appears to be limited mainly by a poor training. The tachypnea observed in these patients at rest and during exercise was unexpected and the reason for adopting such a pattern of breathing is unclear.

Sleep Apnea Syndrome in Endocrine Diseases

It is increasingly recognized that sleep-disordered breathing (SDB) – from snoring to apnea-hypopnea syndrome (SAHS) – can affect patients with various endocrine diseases (ED). Different mechanisms are implied in SDB, promoting either central or, more frequently, obstructive apnea in different ED. In the past, acromegaly and hypothyroidism were first associated with both central and obstructive SAHS. Today, great attention is placed on the complex cause-effect relationship between diabetes mellitus and obstructive SAHS (and vice versa). Symptoms and signs of SAHS may complicate the clinical course of these diseases and should be promptly suspected to detect and possibly treat the accompanying SDB.

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.

Increased QT dispersion: a negative prognostic finding in chronic obstructive pulmonary disease

ObjectiveChronic obstructive pulmonary disease (COPD) is a highly prevalent syndrome, deeply affecting the cardiovascular system as well as the lungs. We investigated the prognostic role of the QT interval and QT dispersion (QTD) in predicting all-cause, respiratory and cardiovascular mortality in COPD, and the relationship between these electrocardiographic parameters and pulmonary function in a prospective longitudinal study.MethodsWe studied 246 COPD patients without significant comorbidities, with a mild to moderate functional impairment, admitted to the Department of Internal Medicine from January 1995 to December 2001, performing a 5-year mean follow-up (5–116 months) up to August 2004. After clinical stabilisation, an electrocardiogram and functional respiratory tests were obtained, allowing measurement of the QT interval and QTD, forced vital capacity (FVC), forced expiratory volume at 1 s (FEV1), inspiratory capacity, FEV1/FVC ratio, partial oxygen pressure and partial carbon dioxide pressure in arterial blood.ResultsAt the end of the follow-up period, 81 patients were dead, 165 still alive; 36 died because of respiratory causes, 23 because of cardio-cerebrovascular events, 21 because of cancer (mainly lung cancer). A significant high incidence of sudden cardiac death was observed. QTD and QTcD showed a significant relationship with respiratory functional parameters. Maximal QT interval, QTcD and QTD appear to be independent predictors of all-cause, cardiovascular and respiratory mortality (relative risk 1.94, 3.22, 2.88, respectively). Age>65 years, partial oxygen pressure <60 mmHg and inspiratory capacity <80% of the predicted value were the only other independent predictive parameters.ConclusionsMaximal QT interval, QTD and QTcD are independent predictors of mortality. A significant incidence of cardiac sudden death was observed. These findings suggest the need for a global and multidisciplinary risk assessment in COPD patients. Intriguing relationships between the QTD and functional respiratory parameters were also observed.