Carlo Pomari

Montelukast 10 mg improves nasal function and nasal response to aspirin in ASA-sensitive asthmatics: a controlled study vs placebo

Aspirin‐induced asthma (AIA) is a clinical syndrome characterized by acute airway reaction to aspirin and other nonsteroidal anti‐inflammatory drugs (NSAIDS). The most recent etiological hypothesises is that an overexpression of the enzyme LTC4 synthase occurs in AIA, with the consequent production of sulfidopeptide leukotrienes (LTs).

COPD prevalence in a north-eastern Italian general population

BACKGROUND COPD prevalence estimates vary mostly depending on different study methodologies. We evaluated the prevalence and clinical features of COPD, as defined by GOLD and ERS/ATS recommendations in a representative sample of Northern Italy general population. METHODS A randomized cross-sectional study was performed. The study participants completed a questionnaire covering: key indicators for considering a diagnosis of COPD, self-reported physician diagnoses of respiratory disease, pharmacological treatment for respiratory disease, indirect costs, occupational and environmental exposures. They also underwent spirometry and physician assessment. RESULTS We evaluated 1236 subjects. Daily respiratory symptoms were experienced by 26.7%. Of this group, only 30.7% had previously performed a spirometry. The overall COPD prevalence was: 11.7% according to GOLD criterion; 9.1% according to LLN criterion; 6.8% according to self-reported physician diagnosis. Of note, 48,8% of subjects with a reported diagnosis of COPD had never undergone a spirometry before the study. CONCLUSIONS Our study provides an estimation of COPD prevalence in a representative sample of Northern Italy general population relying on both clinical symptoms and spirometry outcomes, and describes the different prevalence rates depending on the adopted diagnostic criterion. Spirometry underuse may account for under-diagnosis and misdiagnosis of COPD. It may result in a major impact on quality of life as well as in economic burden.

PD-L1 expression heterogeneity in non-small cell lung cancer: evaluation of small biopsies reliability

Immunotherapy with checkpoint inhibitors, allowing recovery of effector cells function, has demonstrated to be highly effective in many tumor types and represents a true revolution in oncology. Recently, the anti-PD1 agent pembrolizumab was granted FDA approval for the first line treatment of patients with advanced non–small cell lung cancer (NSCLC) whose tumors show PD-L1 expression in ≥ 50% of neoplastic cells and as a second line treatment for patients with NSCLC expressing PD-L1 in ≥1% of neoplastic cells, evaluated with a validated assay. For the large majority of patients such evaluation is made on small biopsies. However, small tissue samples such as core biopsies might not be representative of tumors and may show divergent results given the possible heterogeneous immunoexpression of the biomarker. We therefore sought to evaluate PD-L1 expression concordance in a cohort of 239 patients using tissue microarrays (TMA) as surrogates of biopsies stained with a validated PD-L1 immunohistochemical assay (SP263) and report the degree of discordance among tissue cores in order to understand how such heterogeneity could affect decisions regarding therapy. We observed a discordance rate of 20% and 7.9% and a Cohens κ value of 0.53 (moderate) and 0,48 (moderate) for ≥ 1% and ≥ 50% cutoffs, respectively. Our results suggest that caution must be taken when evaluating single biopsies from patients with advanced NSCLC eligible for immunotherapy; moreover, at least 4 biopsies are necessary in order to minimize the risk of tumor misclassification.

Once-Daily Nebivolol 5mg Does Not Reduce Airway Patency in Patients with Chronic Obstructive Pulmonary Disease and Arterial Hypertension A Placebo-Controlled Crossover Study

AbstractObjective: To evaluate the 24-hour time-course of the effects of a single dose of nebivolol 5mg on airway patency in patients with chronic obstructive pulmonary disease (COPD). Design: Short-term, randomised, double-blind, placebo-controlled, crossover study. Patients: 12 ex-smokers (five males; mean age 63.8 ± 9.8 years, range 46 to 75 years) with stable COPD [mean baseline forced expiratory volume in 1 second (FEV1) 54.9 ± 11.9%; change in FEV1 after salbutamol 200μg = +6.0 ± 3.8% of baseline value] and WHO stage 1–2 mild to moderate arterial hypertension [mean baseline systolic (SBP) and diastolic (DBP) blood pressure, 150.0 ± 12.1 and 97.9 ± 8.4mm Hg, respectively]. Main outcome measures and results: The measured variables were lung function [vital capacity (VC), FEV1, forced vital capacity (FVC), peak expiratory flow (PEF), maximum mid-expiratory flow (MMEF) and specific airway resistance (SRaw)], SBP/DBP and heart rate at baseline (t0), and at 1 (t1), 3 (t3), 6 (t6), 12 (t12) and 24 (t24) hours after the administration of nebivolol or placebo. Exhaled nitric oxide (e-NO) was also assayed at t0, t6 and t24. ANOVA showed that none of the changes from baseline during either 24-hour monitoring period was significant. In terms of the non-respiratory variables, nebivolol did not significantly improve SBP or DBP, although there was a trend towards a reduction in both: the difference in the change in DBP over time between the two treatments was of borderline significance (ANOVA, p < 0.06). Heart rate remained unchanged during both treatments. No significant changes in e-NO were observed throughout the study between placebo and nebivolol treatment. Conclusions: Our results suggest that a single efficacious dose of nebivolol does not affect airway patency in hypertensive patients with COPD, and seem to confirm the broad tolerability margin of this drug in patients with COPD.

Transcutaneous O2 and CO2 Monitoring of Bronchial Responsiveness in FEV1 Non-Responder Asthmatics during Ketotifen and Placebo Treatment

Effects of ultrasonically nebulized distilled water (UNDW) on PtcO2 and PtcCO2 time courses were studied in 26 mild asthmatics (FEV1 non-responders) in basal conditions and monitored after 2, 6, 12 and 18 weeks of randomly allocated treatment with ketotifen 1 mg b.i.d. or placebo. Magnitude and duration of both PtcO2 and PtcCO2 changes due to UNDW inhalation were progressively normalized only by ketotifen. Partial but significant protection against UNDW-induced hyperventilation was achieved after 2 weeks of treatment, complete protection (also against UNDW-induced hypoxia) being achieved later. In view of the CO2 dependency of respiratory drive and the primary structural targets of the hypo-osmotic bronchial challenge employed, these results suggest that ketotifen may affect the mucosal structures of the bronchial airways, thereby acting as a mucosal protective drug.

An Ovine Model of GERD-Induced Bronchoconstriction

The association between bronchial asthma and gastroesophageal reflux disease (GERD) has been reported repeatedly over the last 30 years [1–6], although the issue of cause and effect remains controversial. Reports about a certain kind of relationship between asthma and GERD date back to 1912 when Sir William Osier [7] stated that “asthma attacks may be due to direct irritation of the bronchial mucosa or … indirectly, too, by reflex influences from the stomach”. Dr. Osier’s insight about acid-induced bronchoconstriction remains true today. GERD, the retrograde movement of gastric contents into the esophagus, is a prevalent clinical condition affecting millions of adults around the world. An epidemiologic study performed in the USA in the 1970s suggested that 10% of the population has daily heartburn and more than one-third have intermittent symptoms [8]. More recently, another survey reported that 20% of 800 randomly selected adults had heartburn more than three times a month and another 25% noted heartburn at least once a month [9]. Untreated GERD impairs quality of life and can lead to esophageal complications such as esophagitis, ulceration, stricture and Barrett’s esophagus (replacement of squamous epithelium with columnar epithelium) with its tendency to become malignant [10]. However, the spectrum of problems associated with GERD has expanded to extraesophageal sites [11]. Chronic cough and asthma are two clinical problems caused or triggered by GERD [12, 13]. Furthermore, treatment of GERD may result in marked improvement or even disappearance of symptoms in patients with chronic cough or asthma [12,14]. One potentially critical consideration is that many asthmatic patients do not have classic reflux symptoms but only occasional asymptomatic regurgitation. This condition, although being able to elicit cough and asthma, leaves the clinician unaware that GERD may be playing a crucial role in their patients’ symptoms [15,16].

Clinical use of controlled-release theophylline in chronic airways obstruction

Daily general practice of theophylline dosing in chronic obstructive lung disease seems not strictly to follow therapeutic guidelines. To evaluate the efficacy of such an approach with regard to attaining therapeutic and safe plasma theophylline concentrations and clinical benefit, 103 patients with chronic obstructive lung disease were selected from the computerized database of a post-marketing survey. Dosing of theophylline was found to be independent of reference parameters, i.e. anthropometric data, age and clinical severity of the disease. Standard doses of 400 and/or 600 mg controlled-release theophylline, i.e. 7.9 mg/kg·day resulted in steady-state plasma concentrations of 10–20 μg/ml in 45.1% of patients and 5–10 μg/ml in 52.9% of cases. The increase in forced expiratory volume in 1 s at steady-state, evaluated by the percentage frequency distribution of changes from baseline was significant in all patients. In conclusion, not withstanding the daily therapeutic practice of controlled-release theophylline dosing and, at times, lower than optimal plasma levels, clinical and functional recovery was obtained in a large percentage of cases.

Prevalence and features of asthma–chronic obstructive pulmonary disease overlap in Northern Italy general population

ABSTRACT Objective: There is controversy about the diagnostic criteria, prevalence, symptoms, and spirometry characteristics of asthma–chronic obstructive pulmonary disease (COPD) overlap (ACO). Recent data indicate that the fixed method for diagnosing airway obstruction (AO) may overestimate ACO prevalence in the elderly, and a variable method may be more accurate. We aimed at estimating ACO prevalence in a general population sample and comparing patient and clinical features in subjects with ACO, COPD, and asthma. Methods: We analyzed data from a cross-sectional study estimating COPD prevalence in randomly selected adults aged 20–79 years in Verona, Italy, and estimated prevalence and analyzed characteristics of asthma, COPD, and ACO. ACO was defined as AO (Forced Expiratory Volume in one second–FEV1/ Forced Vital Capacity–FVC < Lower Limit of Normal–LLN), highly positive bronchodilator test (≥15% increase in FEV1 and FVC ≥400 mL), and personal self-reported history of physician diagnosed asthma and atopy. Results: One thousand two hundred and thirty-six patients were included; 207 (16.7%) had asthma, COPD, or ACO (mean ages: 61.2, 59.7, and 57.2 years, respectively). The 3 groups had similar clinical and demographic variables; however, spirometry revealed differences between ACO and COPD patients, particularly post-bronchodilator FEV1 reversibility, which was detected in ACO and asthma patients but not in those with COPD. Conclusion: ACO prevalence in Northern Italy was estimated at 2.1%, in the range of values reported by previous studies. Marked differences between ACO and COPD revealed by spirometry may have important clinical implications in terms of treatment for patients with ACO.

IgG4-related disease: a new challenging diagnosis mimicking lung cancer

IgG4-related disease (IgG4-RD) is a progressive inflammatory disease that might rarely involve only the lungs. We retrospectively reviewed the preoperative, clinical and surgical features of patients with a pathology highly suggestive or probable diagnosis of IgG4-RD without extra-thoracic involvement. Five patients were selected, 2 were operated on the right side. Positron emission tomography-computed tomography (PET-CT) showed an uptake in all the patients (median 5.5), and 2 patients had an uptake at the thoracic lymph nodes. Two diagnoses were made through a CT-guided needle biopsy, while 3 were determined based on a lung wedge resection. The levels of serum IgG4 were elevated (>1.35 g/dl) in all the patients. Two patients had a highly suggestive diagnosis of IgG4-RD, and 3 patients had a probable diagnosis of IgG4-RD. The differential diagnosis between IgG4-RD and lung malignancies based only on radiological features is challenging and often requires histological confirmation. A careful preoperative workup and a multidisciplinary approach to PET-positive nodules might help to avoid unnecessary major lung resections.

Indwelling Pleural Catheters: A Clinical Option in Trapped Lung.

Malignant pleural effusion (MPE) symptoms have a real impact on quality of life. Surgical approach through video-assisted thoracic surgery provides a first step in palliation. In patients unfit for general anesthesia, awake pleuroscopy represents an alternative. Sclerosing agents can be administered at the bedside through a chest tube. Ideal treatment of MPE should include adequate long-term symptom relief, minimize hospitalization, and reduce adverse effects. Indwelling pleural catheter (IPC) allows outpatient management of MPE through periodic ambulatory fluid drainage. IPC offers advantages over pleurodesis in patients with poor functional status who cannot tolerate pleurodesis or in patients with trapped lungs.