Mario Polverino

Xolair in asthma therapy: an overview.

Asthma is a chronic lung inflammatory disease affecting from 5 to 10% of the population. It generally appears with periods of crisis alternating with free periods, but inflammation is always present. Allergic asthma manifests with paroxysmal crisis of bronchospasm, hissing-like respiratory noises, dyspnea, and respiratory distress syndrome. Different studies have shown an increase of IgE serum levels in subjects suffering from allergic asthma. Xolair is a monoclonal antibody that binds the Cε3 domain of IgEs, inducing a conformational change of the immunoglobulin, a concealment of FcεRI and FcεRII receptors binding sites, thus precluding binding by IgEs and therefore stopping the release of inflammation mediators. Xolair is indicated as add-on therapy to improve asthma control in adult and adolescent patients (12 years of age and above) suffering from severe persistent allergic asthma. The aim of this review is 1) to explore the safety and tolerability of Xolair in asthma therapy and 2) to examine recent important developments focusing on treatment strategies of asthma with Xolair.

Anatomy and neuro-pathophysiology of the cough reflex arc.

Coughing is an important defensive reflex that occurs through the stimulation of a complex reflex arc. It accounts for a significant number of consultations both at the level of general practitioner and of respiratory specialists. In this review we first analyze the cough reflex under normal conditions; then we analyze the anatomy and the neuro-pathophysiology of the cough reflex arc. The aim of this review is to provide the anatomic and pathophysiologic elements of evaluation of the complex and multiple etiologies of cough.

Pulmonary concentrations of dirithromycin and erythromycin during acute exacerbation of mild chronic obstructive pulmonary disease

We compared the concentrations of dirithromycin and erythromycin at steady state in serum and the intrapulmonary region in patients suffering from acute exacerbation of mild chronic obstructive pulmonary disease. Twenty patients received dirithromycin, 500 mg given orally once daily for five consecutive days. The other 20 patients were treated with erythromycin base, which was administered orally four times daily at a total daily dose of 1000 mg for seven days. All patients were divided into eight groups, with five subjects in each group, according to sampling times (2, 4, 8, and hrs after the last dose) and treatment. After the erythromycin treatment mean serum concentrations were higher than those of dirithromycin treatment mean serum concentrations were higher than those of dirithromycin for upto 4 hours, but they were undetectable 24 hours after the last dose. At all time periods, the concentrations of dirithromycin in bronchial secretion, bronchial mucosa and epithelial lining fluid were greater than the concentration in serum. Concentrations of erythromycin were always lower than those of dirithromycin in the explored pulmonary sites. Our data demonstrated that a five day course of 500 mg of dirithromycin once daily induced higher concentrations and longer persistence in the various potential sites of pulmonary infection than a seven day course of 250 mg of erythromycin every 6 hrs. The shorter duration of therapy and the once daily dosing with good efficacy against common respiratory pathogens would be advantageous for patients and would be likely to promote better patient compliance and acceptability.

Current best practice in pulmonary rehabilitation for chronic obstructive pulmonary disease.

Chronic obstructive pulmonary disease (COPD) is a chronic condition that negatively affects several patient-centered outcomes. Among these, exercise capacity, dyspnea, and quality of life are the most relevant. In this article, factors contributing to exercise limitation, increase in exercise-induced dyspnea, quality of life deterioration, and other pathophysiological aspects in patients with COPD are analyzed in detail. Pulmonary rehabilitation (PR) is an evidence-based, multidisciplinary, and comprehensive intervention for patients with chronic respiratory diseases who are symptomatic and often have decreased daily life activities. PR has been clearly shown to induce favorable and long-lasting effects on all patient-centered outcomes. In addition, PR appears to have positive (even if not conclusively demonstrated) effects on other important outcomes in patients with COPD: number and severity of exacerbations, healthcare resource utilization, and survival. The organization of PR treatment, its components, outcome assessment, and future directions are discussed in light of the most robust scientific evidence.

The AIMAR recommendations for early diagnosis of chronic obstructive respiratory disease based on the WHO/GARD model*

Respiratory diseases in Italy already now represent an emergency (they are the 3rd ranking cause of death in the world, and the 2nd if Lung cancer is included). In countries similar to our own, they result as the principal cause for a visit to the general practitioner (GP) and the second main cause after injury for recourse to Emergency Care. Their frequency is probably higher than estimated (given that respiratory diseases are currently underdiagnosed). The trend is towards a further increase due to epidemiologic and demographic factors (foremost amongst which are the widespread diffusion of cigarette smoking, the increasing mean age of the general population, immigration, and pollution). Within the more general problem of chronic disease care, chronic respiratory diseases (CRDs) constitute one of the four national priorities in that they represent an important burden for society in terms of mortality, invalidity, and direct healthcare costs. The strategy suggested by the World Health Organization (WHO) is an integrated approach consisting of three goals: inform about health, reduce risk exposure, improve patient care. The three goals are translated into practice in the three areas of prevention (1-primary, 2-secondary, 3-tertiary) as: 1) actions of primary (universal) prevention targeted at the general population with the aim to control the causes of disease, and actions of Predictive Medicine - again addressing the general population but aimed at measuring the individual’s risk for disease insurgence; 2) actions of early diagnosis targeted at groups or - more precisely - subgroups identified as at risk; 3) continuous improvement and integration of care and rehabilitation support - destined at the greatest possible number of patients, at all stages of disease severity. In Italy, COPD care is generally still inadequate. Existing guidelines, institutional and non-institutional, are inadequately implemented: the international guidelines are not always adaptable to the Italian context; the document of the Agency for Regional Healthcare Services (AGE.NA.S) is a more suited compendium for consultation, and the recent joint statement on integrated COPD management of the three major Italian scientific Associations in the respiratory area together with the contribution of a Society of General Medicine deals prevalently with some critical issues (appropriateness of diagnosis, pharmacological treatment, rehabilitation, continuing care); also the document “Care Continuity: Chronic Obstructive Pulmonary Disease (COPD)” of the Global Alliance against chronic Respiratory Diseases (GARD)-Italy does not treat in depth the issue of early diagnosis. The present document – produced by the AIMAR (Interdisciplinary Association for Research in Lung Disease) Task Force for early diagnosis of chronic respiratory disease based on the WHO/GARD model and on available evidence and expertise –after a general examination of the main epidemiologic aspects, proposes to integrate the above-mentioned existing documents. In particular: a) it formally indicates on the basis of the available evidence the modalities and the instruments necessary for carrying out secondary prevention at the primary care level (a pro-active,‘case-finding’approach; assessment of the individual’s level of risk of COPD; use of short questionnaires for an initial screening based on symptoms; use of simple spirometry for the second level of screening); b) it identifies possible ways of including these activities within primary care practice; c) it places early diagnosis within the “systemic”, consequential management of chronic respiratory diseases, which will be briefly described with the aid of schemes taken from the Italian and international reference documents.

Impaired exercise performance in systemic sclerosis and its clinical correlations

Objectives: To investigate the prevalence of impaired exercise performance as assessed by a standardized cardiopulmonary exercise test (CPET) in systemic sclerosis (SSc) and to identify the associated disease features. Methods: Forty-six SSc patients were enrolled and evaluated for clinical and serological SSc subset, extent of skin and internal organ involvement, and disease activity and severity. Exercise performance was subsequently evaluated in these patients and in 23 healthy individuals matched for sex and age, using a standardized CPET. Results: Exercise performance, measured by maximum oxygen uptake ( max < 80% of predicted value), was found to be impaired in 43/46 patients. Stepwise regression analysis showed that max adjusted for body weight ( max/kg) was independently correlated with the severity of heart (p = 0.001) and lung (p = 0.013) involvement, left ventricular diastolic dysfunction (p = 0.009), and the Health Assessment Questionnaire Disability Index (HAQ-DI) score (p = 0.016). Conclusions: This study demonstrates that physical disability contributes significantly to the development of impaired exercise performance in SSc patients. Cardiopulmonary exercise testing may be included among the battery of tests used to determine the severity of SSc.

Exercise capacity and cytochrome oxidase activity in muscle mitochondria of COPD patients

Skeletal muscle dysfunction (SMD) often occurs in patients with COPD, affecting their quality of life and mitochondrion is one of the cellular organelles involved in the pathogenesis of SMD in COPD. The aim of this study was to investigate exercise capacity and mitochondria skeletal muscle oxidative processes using a pilot study, with 20 COPD patients and 10 healthy subjects, prior to and following LABA treatment. The two groups were similar for BODE (2-7) and GOLD stages (2-3), and no one was cachectic or more symptomatic. The patients were randomized according to a distribution list. The Cycle Ergometry test with tau evaluation was used to determine exercise capacity, while a skeletal muscle biopsy for cytochrome oxidase (CytOX) activity evaluation was used to determine mitochondria skeletal muscle oxidative processes. In six of the COPD treated patients the individual values of tau and CytOX activity showed inversely parallel changes with a significant relationship between the tau values and the CytOX activity. No significant differences in tau values were observed in healthy subjects. In conclusion, LABA treatment may improve skeletal muscle oxidative processes, enhancing the CytOX activity and, at least in some COPD patients, such effects could be strictly linked to the kinetic exchanges occurring at skeletal muscle level, implying an important link between the regulation of oxygen uptake, energy production and the exercise capacity of these patients. Nevertheless, further studies are required and a better understanding of the mechanism(s) underlying LABA effects might allow us to identify or unmask new therapeutic target(s) in such patients.

C-reactive protein and carotid intima-media thickness in children with sleep disordered breathing.

STUDY OBJECTIVES Obesity is a risk factor for sleep disordered breathing (SDB) in children. Plasma levels of high-sensitivity C-reactive protein (Hs-CRP) are predictive of cardiovascular morbidity in adults, and CRP levels are associated with over-weight. Increased carotid intima-media thickness (IMT) is associated with several cardiovascular risk factors. We evaluated the effect of SDB on CRP levels and IMT in lean and obese children not selected for snoring. METHODS 101 children (age 5-15 years) attending a weight clinic or scheduled for routine visit. IMT was measured with quantitative B-mode ultrasound scans. The apnea-hypopnea index (AHI) was measured overnight: AHI < 1 defined controls, AHI ≥ 1 to < 5 = mild SDB, and AHI ≥ 5 = obstructive sleep apnea (OSA). RESULTS AHI was significantly associated with Hs-CRP concentration (r = 0.32, p = 0.002) in all 101 children irrespective of age and sex. Body mass index (BMI) was higher in OSA children than controls (25.5 ± 7.0 vs 22.1 ± 6.9, p = 0.05). Obese children had 3.3 times more probability of having OSA (HR 3.3, 95% CI 1.2-9.3, p = 0.02) than lean children. Hs-CRP values were significantly higher in children with OSA than in children without (p = 0.011), but not when BMI z-score was added as covariate. IMT was not associated with AHI or SDB. CONCLUSIONS The results of this study suggest an association between OSA and Hs-CRP concentrations (mainly mediated by overweight and obesity), but not between OSA and subclinical atherosclerosis. There is scope for prevention in childhood before OSA syndrome causes the irreversible damage to arteries observed in adult patients.

Sexual intercourse and respiratory failure

Sexual activity is an important component of quality of life in patients suffering from chronic illnesses. To our knowledge, the effects of sexual activity on gas exchange in patients with respiratory failure have not been yet studied. To such an extent, we evaluated the oxygen saturation (SaO2), by a pulse oxymeter, during three different sexual performances in a 63-yr-old patient affected by chronic obstructive pulmonary disease (COPD) on long-term oxygen therapy (LTOT). The sexual performances were divided in four periods: basal, sex, 10 min after sex and relax. In each performance during sex, we observed a significant increase of either heart rate (HR) or SaO2, with the highest value of the latter achieved within the 10 min of the post-sex period. SaO2 returned to basal value (pre-sex) by the end of the relax period. We conclude that the observed improvement of SaO2 during sexual activity might be due to a better ventilation/perfusion ratio (V/Q) obtained for either an increase of ventilation (hyperventilation) and perfusion (tachycardia), without significant muscle expenditure.

Idiopathic pulmonary fibrosis and coronary artery disease

Idiopathic pulmonary fibrosis (IPF) is defined as a chronic fibrosing interstitial disease of unknown cause, limited to the lungs, and associated with the histopathologic and/or radiologic pattern of usual interstitial pneumonia (UIP); it generally progresses into respiratory failure and death. Although progression of the disease is the most common cause of death, there are increasing reports of its association with other pathologies has been reported: e.g., IPF patients seem more susceptible to cardiovascular diseases. Therefore, other pathologies might also influence the natural course.In this paper, we describe a case of IPF and coronary artery disease (CAD). We emphasize the importance of cardiopulmonary exercise test (CPET) as a useful procedure to monitor disease progression in IPF patients. We also stress the importance of a careful analysis of variables measured for an accurate interpretation of the clinical picture and an improvement of the clinical management of patients. Moreover, we suggest that a careful assessment of CPET parameters may additionally help in the early detection of high cardiovascular ischemic risk.