Sustained remission induced by 2 years of treatment with benralizumab in patients with severe eosinophilic asthma and nasal polyposis.

BACKGROUND AND OBJECTIVE: Several randomized controlled trials (RCTs) have shown that benralizumab is characterized by a good profile of efficacy and safety, thereby being potentially able to elicit clinical remission on-treatment of severe eosinophilic asthma (SEA). The main goal of this multicentre observational study was to verify the effectiveness of benralizumab in inducing a sustained remission on-treatment of SEA in patients with or without comorbid chronic rhinosinusitis with nasal polyps (CRSwNP). METHODS: Throughout 2 years of treatment with benralizumab, a four-component evaluation of sustained remission of SEA was performed, including the assessment of SEA exacerbations, use of oral corticosteroids (OCSs), symptom control and lung function. RESULTS: The present study recruited 164 patients suffering from SEA. After 24 months of add-on biological therapy with benralizumab, 69 (42.1%) achieved the important target of sustained remission on-treatment (exacerbation rate = 0, OCS dose = 0, pre-bronchodilator FEV1 ≥80% pred., ACT score ≥ 20). During the same period, a persistent improvement of CRSwNP (SNOT-22 < 30, NP recurrence = 0) was observed in 33 (40.2%) out of 82 subjects with concomitant NP. The latter comorbidity and post-bronchodilator reversibility of airflow limitation were two independent predictors of sustained remission on-treatment (OR = 2.32, p < 0.05 and OR = 5.59, p < 0.01, respectively). CONCLUSION: Taken together, the results of this real-life clinical investigation indicate that benralizumab can induce a sustained remission on-treatment of SEA, especially in those patients with comorbid CRSwNP and reversible airflow limitation.

Fully covered self-expandable metal stent in tracheobronchial disorders: clinical experience.

BACKGROUND: The third-generation fully covered self-expandable metallic stent (SEMS) has been developed to solve the problems of difficult removal and in-stent granuloma formation related to the uncovered or partially covered type. There are few written reports about the performance of this type of stents with early encouraging results. OBJECTIVES: To report and analyse our experience with the Silmet® stent in the management of malignant and benign tracheobronchial disorders. METHODS: We retrospectively reviewed medical records of patients who underwent fully covered SEMS Silmet placement at the Interventional Pulmonology Unit, La Maddalena Cancer Center, Palermo, Italy, between May 2010 and August 2013. RESULTS: Stents were placed in 52 patients with malignant (n = 49) and benign airway obstruction (n = 2) and broncho-oesophageal fistula (n = 1). SEMSs were inserted into the trachea (n = 19), the main bronchi (n = 21) and the peripheral bronchi (n = 31). Besides 1 procedural dislocation, the deployment was successful in all patients with an immediate significant improvement of symptoms (Barthel Index p < 0.001; Medical Research Council score p < 0.001). A radiographic improvement was detected in 48% of patients. The mean follow-up duration was 119 ± 120 days (range 22-549 days). Complications observed were: migration (7.6%), tumour overgrowth (15%), infections (5.7%), granulation tissue formation (3.8%) and mucus plug (3.8%). CONCLUSIONS: The Silmet stent is effective, safe and simple to implant and remove. We suggest its use in cases of tight stenoses, in the treatment of small- to medium-caliber airways or in cases of tortuous airways.

Real-life effects of dupilumab in patients with severe type 2 asthma, according to atopic trait and presence of chronic rhinosinusitis with nasal polyps.

Background: The efficacy of dupilumab as biological treatment of severe asthma and chronic rhinosinusitis with nasal polyps (CRSwNP) depends on its ability to inhibit the pathophysiologic mechanisms involved in type 2 inflammation. Objective: To assess in a large sample of subjects with severe asthma, the therapeutic impact of dupilumab in real-life, with regard to positive or negative skin prick test (SPT) and CRSwNP presence or absence. Methods: Clinical, functional, and laboratory parameters were measured at baseline and 24 weeks after the first dupilumab administration. Moreover, a comparative evaluation was carried out in relation to the presence or absence of SPT positivity and CRSwNP. Results: Among the 127 recruited patients with severe asthma, 90 had positive SPT, while 78 reported CRSwNP. Compared with the 6 months preceding the first dupilumab injection, asthma exacerbations decreased from 4.0 (2.0-5.0) to 0.0 (0.0-0.0) (p < 0.0001), as well as the daily prednisone intake fell from 12.50 mg (0.00-25.00) to 0.00 mg (0.00-0.00) (p < 0.0001). In the same period, asthma control test (ACT) score increased from 14 (10-18) to 22 (20-24) (p < 0.0001), and sino-nasal outcome test (SNOT-22) score dropped from 55.84 ± 20.32 to 19.76 ± 12.76 (p < 0.0001). Moreover, we observed relevant increases in forced expiratory volume in one second (FEV1) from the baseline value of 2.13 L (1.62-2.81) to 2.39 L (1.89-3.06) (p < 0.0001). Fractional exhaled nitric oxide (FeNO) values decreased from 27.0 ppb (18.0-37.5) to 13.0 ppb (5.0-20.0) (p < 0.0001). These improvements were quite similar in subgroups of patients characterized by SPT negativity or positivity, and CRSwNP absence or presence. No statistically significant correlations were detected between serum IgE levels, baseline blood eosinophils or FeNO levels and dupilumab-induced changes, with the exception of FEV1 increase, which was shown to be positively correlated with FeNO values (r = 0.3147; p < 0.01). Conclusion: Our results consolidate the strategic position of dupilumab in its role as an excellent therapeutic option currently available within the context of modern biological treatments of severe asthma and CRSwNP, frequently driven by type 2 airway inflammation.

Tracheal stent to repair tracheal laceration after a double-lumen intubation.

A 59-year-old woman was referred for a diagnostic video thoracoscopy under general anesthesia. At the end of the procedure, the patient presented with subcutaneous emphysema and cyanosis, abdominal distension, and bradycardia. A rigid bronchoscopy showed a longitudinal laceration in the pars membranacea of the trachea. A tracheal silicon stent was positioned on an emergency basis. She was intubated, positioning the tracheal tube cuff distal of the stent under bronchoscopic vision. A computed tomographic scan performed immediately after the procedure showed left pneumothorax, pneumoperitoneum, pneumopericardium, and diffuse subcutaneous emphysema. The subsequent course of the patient was uneventful. The patient was discharged home on postoperative day 4. After 1 year, the stent was removed with the evidence of complete trachel healing.

C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR) as inflammation markers in elderly patients with stable chronic obstructive pulmonary disease (COPD).

Erythrocyte sedimentation rate (ESR) might represent a less expensive alternative to C-reactive protein (CRP) as a marker of systemic inflammation in stable chronic obstructive pulmonary disease (COPD). We tried to verify this hypothesis in 223 consecutive outpatients aged 65 years or more with stable COPD enrolled in a multicenter observational study. Patients were grouped according to normal/increased ESR/CRP values and groups were compared with regard to clinical and laboratory characteristics. Correlations between CRP, ESR and selected variables of interest were assessed by Spearman's ζ-test and multivariate linear regression analysis. CRP was weakly and inversely correlated with the forced expiratory volume in the first second (FEV1%) (Spearman's ζ = -0.15; p < 0.027), while ESR was not (Spearman's ζ = -0.05; p = 0.411). The highest prevalence of anemia and hypoalbuminemia and the lowest FEV1% were recorded in high ESR-high CRP group. For anemia B = 14.180 ± 3.521 (± S.E.M.); p = 0.001 and hypoalbuminemia B = 10.241 ± 3.790; p = 0.007 qualified as significant independent correlates of ESR values, while only FEV1 remained significantly associated with CRP values (B = -0.570 ± 0.258; p = 0.028). In conclusion, CRP, but not ESR, shows a weak correlation with COPD severity, while anemia and hypoalbuminemia are main correlates of high ESR. Neither ESR, nor CRP qualify as reliable markers of COPD severity and seem to reflect the effects of different determinants.

Patient perspectives in the management of asthma: improving patient outcomes through critical selection of treatment options.

Asthma is a chronic inflammatory disorder of the airways that requires long-term treatment, the goal of which is to control clinical symptoms for extended periods with the least possible amount of drugs. International guidelines recommend the addition of an inhaled long-acting beta2-agonist (LABA) to a low- to medium-dose inhaled corticosteroid (ICS) when low doses of ICS fail to control asthma symptoms. The fixed combined administration of ICS/LABA improves patient compliance, reducing the risk of therapy discontinuation. The relative deposition pattern of the inhaled drug to the target site is the result of a complex interaction between the device used, the aerosol formulation and the patient's adherence to therapy. Different inhalation devices have been introduced in clinical practice over time. The new hydrofluoroalkane (HFA) solution aerosols allow for the particle size to be modified, thus leading to deeper penetration of the medication into the lung. The Modulite((R)) technology allows for the manipulation of inhaled HFA-based solution formulations, such as the fixed beclomethasone/formoterol combination, resulting in a uniform treatment of inflammation and bronchoconstriction. The success of any anti-asthmatic treatment depends on the choice of the correct device and the adherence to therapy.

Chronic renal failure: a neglected comorbidity of COPD.

BACKGROUND: To the best of our knowledge, the association between COPD and chronic renal failure (CRF) has never been assessed. Lean mass is frequently reduced in COPD, and the glomerular filtration rate (GFR) might be depressed in spite of normal serum creatinine (concealed CRF). We investigated the prevalence and correlates of both concealed and overt CRF in elderly patients with COPD. METHODS: We evaluated 356 consecutive elderly outpatients with COPD enrolled in the Extrapulmonary Consequences of COPD in the Elderly Study and 290 age-matched outpatients free from COPD. The GFR was estimated using the Modification of Diet in Renal Disease Study Group equation. Patients were categorized as having normal renal function (GFR > or = 60 mL/min/1.73 m(2)), concealed CRF (normal serum creatinine and reduced GFR), or overt CRF (increased serum creatinine and reduced GFR). Independent correlates of CRF were investigated by logistic regression analysis. RESULTS: The prevalence of concealed and overt CRF in patients with COPD was 20.8% and 22.2%, respectively. Corresponding figures in controls were 10.0% and 13.4%, respectively. COPD and age were significantly associated with both concealed CRF (COPD: odds ratio [OR] = 2.19, 95% CI = 1.17-4.12; age: OR = 1.06, 95% CI = 1.04-1.09) and overt CRF (COPD: OR = 1.94, 95% CI = 1.01-4.66; age: OR = 1.06, 95% CI = 1.04-1.10). Diabetes (OR = 1.96, 95% CI = 1.02-3.76), hypoalbuminemia (OR = 2.83, 95% CI = 1.70-4.73), and muscle-skeletal diseases (OR = 1.78, 95% CI = 1.01-3.16) were significant correlates of concealed CRF. BMI (OR = 1.05, 95% CI = 1.01-1.10) and diabetes (OR = 2.25, 95% CI = 1.26-4.03) were significantly associated with overt CRF. CONCLUSIONS: CRF is highly prevalent in patients with COPD, even with normal serum creatinine, and might contribute to explaining selected conditions such as anemia that are frequent complications of COPD.