M. P. Foschino Barbaro

Low sleep quality and daytime sleepiness in obese patients without obstructive sleep apnoea syndrome

Abstract.  Resta O, Foschino‐Barbaro MP, Bonfitto P, Giliberti T, Depalo A, Pannacciulli N, De Pergola G (Respiratory Pathophysiology, University of Bari, School of Medicine, Bari, Italy; University of Foggia, School of Medicine, Foggia, Italy; and Internal Medicine, Endocrinology, and Metabolic Diseases, University of Bari, Bari, Italy). Low sleep quality and daytime sleepiness in obese patients without obstructive sleep apnoea syndrome. J Intern Med 2003; 253: 536–543.

High prevalence of previously unknown subclinical hypothyroidism in obese patients referred to a sleep clinic for sleep disordered breathing

BACKGROUND AND AIM To evaluate the prevalence of previously unknown hypothyroidism in adult male and female patients with a wide range of body mass index (BMI) values, referred to a Sleep Clinic because of sleep disordered breathing (SDB). METHODS AND RESULTS Serum concentrations of thyroid stimulating hormone (TSH) and free thyroxin (fT4), as well as forced vital capacity (FVC), PaO2, PaCO2, the Epworth sleepiness scale (ESS), respiratory disturbance index (RDI), loud snoring, and the percentage of total sleep time (TST) with <90% oxyhemoglobin saturation (TST(saO2<90%)) were measured in 78 overweight and obese adult subjects with no previous diagnosis of hypothyroidism (age: 18-72 years). The prevalence of previously undiagnosed subclinical hypothyroidism in the population as a whole was 11.5%. BMI, TSH and ESS were significantly higher in the hypothyroid than the euthyroid subjects, but there was no significant between-group difference in RDI, TST(saO2<90%) or the other investigated variables, including the prevalence of obstructive sleep apnea (OSA). Among the hypothyroid individuals, BMI, neck circumference, ESS, RDI and TST(Sao2<90%) were significantly higher in those with than in those without OSA. Furthermore, there was a clear trend towards a lower FVC% and higher snoring score in the OSA patients. CONCLUSIONS Our results demonstrate a higher prevalence of hypothyroidism than that commonly reported in overweight and obese individuals referred to a Sleep Clinic for polysomnography because of SDB, thus suggesting that thyroid function should be evaluated in all obese patients suffering from SDB despite economic concerns.

Early and late failure of noninvasive ventilation in chronic obstructive pulmonary disease with acute exacerbation

Background  Despite recent encouraging results, the use of noninvasive ventilation (NIV) in the management of acute exacerbations in chronic obstructive pulmonary disease (COPD), complicated by acute respiratory failure (ARF), is not always successful. Failure of NIV may require an immediate intubation after a few hours (usually 1–3) of ventilation (‘early failure’) or may result in clinical deterioration (one or more days later) after an initial improvement of blood gas tension and general conditions (‘late failure’).

Menopausal asthma: A new biological phenotype?

To cite this article: Foschino Barbaro MP, Costa VR, Resta O, Prato R, Spanevello A, Palladino GP, Martinelli D, Carpagnano GE. Menopausal asthma: a new biological phenotype? Allergy 2010; 65: 1306–1312.

Repeated virus identification in the airways of patients with mild and severe asthma during prospective follow-up

To cite this article: Turchiarelli V, Schinkel J, Molenkamp R, Foschino Barbaro MP, Carpagnano GE, Spanevello A, Lutter R, Bel EH, Sterk PJ. Repeated virus identification in the airways of patients with mild and severe asthma during prospective follow‐up. Allergy 2011; 66: 1099–1106.

Diurnal PaCO2 tension in obese women: relationship with sleep disordered breathing.

OBJECTIVE: Several obese subjects show a wide array of respiratory disturbances during sleep due to an increased upper-airway resistance. The aim of the present study was to evaluate diurnal PaCO2 tension in nonsmoking obese women and the possible relationship of this parameter with the presence of sleep disordered breathing (SDB).DESIGN: Cross-sectional study of PaCO2 tension in obese women.PATIENTS AND METHODS: A total of 91 nonsmoking obese women (BMI ≥30 kg/m2, aged 42.8±15.7 y) were recruited and evaluated for general and anthropometric parameters, respiratory function, sleep-related symptoms, and sleep disorders of breathing.RESULTS: A total of 10 subjects (10.9%) had diurnal hypercapnia (PaCO2≥43 mmHg). Age, BMI, neck circumference, apnoea/hypopnoea index, and nocturnal desaturation (expressed as TSTSaO2<90%; TSTSaO2<90%=percentage of total sleep time with oxyhaemoglobin saturation <90%) were significantly higher in obese patients with diurnal hypercapnia, compared to normocapnic women. Moreover, hypercapnic patients had reduced forced expiratory volume in 1 s compared to normocapnic individuals. By using multiple regression analysis, the best fitting model (r=0.62, P<0.001) for predicting diurnal PaCO2 tension in the study population showed that 24.23% of the variance may be explained by TSTSaO2<90%, according to the equation: PaCO2=0.09 age+0.07 TSTSaO2<90%+33.00.CONCLUSIONS: This study suggests that severity of SDB is the most important factor in determining diurnal PaCO2 tension in apparently healthy nonsmoking obese women.

The role of obstructive sleep apnea syndrome and obesity in determining leptin in the exhaled breath condensate

Leptin plays a key role in obstructive sleep apnea syndrome (OSAS). Leptin production in human airways has been previously evaluated by measuring leptin concentration in the exhaled breath condensate and in the induced sputum. The aim was to study leptin expression in the cells of induced sputum and in exhaled breath condensate of subjects with OSAS. Moreover, leptin concentrations in the blood were measured in the same groups of subjects. We enrolled four groups of patients: (1) obese patients with OSAS (OO); (2) non-obese patients with OSAS (NOO); (3) obese patients without OSAS (ONO); and (4) non-obese subjects without OSAS (C). Leptin expression was evaluated by immunocytochemistry in the sputum cells of the enrolled subjects. The concentrations of leptin in the exhaled breath condensate and plasma were measured by using a specific enzyme immunoassay. Leptin protein expression and the percentage of macrophages and neutrophils expressing leptin were higher in the induced sputum of OO, NOO and ONO patients than in C. Leptin concentrations in the exhaled breath condensate were significantly higher in OO patients (5.12 (3.8-6.6) ng ml(-1)) than in NOO (4.1 (3.9-5.2) ng ml(-1)) and ONO (4.2 (3.6-5.0) ng ml(-1)) patients. The concentration of leptin in plasma was significantly more elevated in OO (36 (24-65.9) ng ml(-1)) than in NOO (30.2 (12.4-51.4) ng ml(-1)), whereas it was not significantly different in ONO patients. This study showed that leptin in sputum and in the exhaled breath condensate is higher in obese patients with OSAS than in obese subjects without OSAS. Moreover, different mechanisms for determining leptin concentrations in the exhaled breath condensate and the blood are suggested.

Fluticasone propionate/formoterol: A fixed-combination therapy with flexible dosage

International guidelines describe asthma control as the main outcome of asthma management. Prevention of symptoms, improved quality of life, and reduction of exacerbations are the main components, consequently decreasing health care costs. However, many of these objectives remain unmet in real life: several surveys show that a large proportion of asthmatic patients are not well controlled despite the efficacy of current available treatment. Several randomized controlled clinical trials indicate that combining inhaled corticosteroids and long-acting β2-agonists, by means of a single inhaler, greatly improves the management of the disease. The results of 9 multicenter phase III clinical studies demonstrate that the fixed combination of fluticasone propionate/formoterol in a single inhaler is effective in terms of lung function and symptom control. These studies highlight the dose flexibility, safety and tolerability of this new inhaled combination. These characteristics meet the recommendations of international guidelines, and the preferences of respiratory physicians who identified these aspects as critical components of a successful asthma therapy. Combination of fluticasone propionate/formoterol in a single inhaler provides potent anti-inflammatory activity of fluticasone propionate and rapid onset of action of the β2-agonist formoterol making this association a viable treatment option both in terms of effectiveness and compliance.

Evidence of lower oxidative stress in the air spaces of patients with reversible COPD.

The mechanism responsible for the reversibility of airflow limitation in stable chronic obstructive pulmonary disease (COPD) patients is unknown. The aim of this study is to assess the relationship between the reversibility of airflow limitation, the redox balance and the inflammatory cells in the sputum of patients with stable COPD. For this purpose we examined 15 normal healthy control subjects and 20 nonatopic COPD patients. The COPD patients were divided into two groups: reversible COPD (increase in FEV1>200 ml and/or ≥12% after 200 μg of inhaled salbutamol) or non-reversible COPD. GSH, GSSG were measured in induced sputum and blood. Protein carbonyls were evaluated by WB in sputum and IL-4 and IL-6 and TNF-α in plasma and sputum. GSH oxidation and protein oxidation were lower in reversible COPD patients than in those with no reversibility. The sputum eosinophil count was significantly higher in the reversible group than in the non-reversible group, and IL-4 concentration was higher in the same patients both in sputum and in plasma. In contrast, IL-6 and TNF-α were increased in non-reversible COPD patients in both biological samples. We conclude that airflow reversibility in COPD patients is associated with airway oxidative stress and activation of eosinophil inflammatory pattern in sputum and blood, suggesting that these patients could respond to specific pharmacological treatment.

Microsatellite alterations suggestive of organ-specific asthma and atopy in exhaled breath condensate.

Several genetic linkage studies demonstrated the existence of organ-specific disease susceptibility genes which may induce asthma and atopy (1). In particular, chromosomes 6p and 14q seem to host asthma/atopy susceptibility genes (2). Microsatellite alterations (MAs) in these regions were detected in sputum cells of asthmatics (3). The MAs can serve as a valid tool to discriminate between asthma and COPD patients (4). MAs are undetectable in nasal cytology samples from patients with allergic rhinitis as bronchial asthma MAs are specific for disease target organ (5). The possibility to analyze MAs in exhaled breath condensate (EBC) was demonstrated. The method was validated by the comparative study of the EBC DNA MAs and paired lung tissue DNA, allowing the use of this sample in lung disease genetic studies (6). The aim of the study was to investigate MAs of chromosomes 6p and 14q in EBC DNA of a group of asthmatics with atopy (AAs), a group of nonatopic asthmatics (ANAs) and a group of nonasthmatic atopics (As), and to verify whether atopy and asthma have different genetic traits. Twenty-eight consecutive AAs, 13 ANAs, 15 As and 15 healthy subjects (HS) were enrolled (Table 1). The diagnosis of asthma and the assessment of its severity were performed according to GINA. Peripheral whole blood (WB) and EBC were collected from each patient. DNA from WB and EBC was extracted by using QIAmp DNA mini Kit (Qiagen, Mican, Italy). Five fluorescence labeled markers located at chromosomes 14q (D14S258, D14S588, D14S292) and 6p (D6S2223, D6S263) were used to evaluate LOH and MI. DNA was amplified by the PCR. The samples were analyzed by capillary electrophoresis on ABI PRISM 310 (Applied Biosystems, Monza, Italy). Good quality DNA in terms of integrity and amount (mean quantity: 20 ng/ ll) was obtained from all EBC samples. None of the HS exhibited genetic alteration of the five markers tested supporting Paraskakis’ hypothesis that these markers are disease-specific (4). MAs in WB-DNA were absent. The microsatellites D14S292 and D6S2223 drive the susceptibility to atopy and asthma, respectively, other microsatellites are involved in both phenotypes. The increased number of MAs is associated with a declined lung function, severe asthma and high degree of atopy. The AAs exhibited the highest percentages of MAs at 6p and 14q. The highest number of MAs was found in the EBC DNA of AAs confirming the results obtained from sputum DNA (4). In accordance with Parashakis et al. (4) the correlation Exhaled microsatellite alterations at chromosomes 6p and 14q are suggestive of organ-specific asthma and atopy. ALLERGY Net