Sildenafil in severe pulmonary hypertension associated with chronic obstructive pulmonary disease: A randomized controlled multicenter clinical trial.

BACKGROUND: Pulmonary hypertension (PH) is a well-known independent prognostic factor in chronic obstructive pulmonary disease (COPD) and a sufficient criterion for lung transplant candidacy. Limited data are currently available on the hemodynamic and clinical effect of phosphodiesterase 5 inhibitors in patients with severe PH associated with COPD. This study assessed the effect of sildenafil on pulmonary hemodynamics and gas exchange in severe PH associated with COPD. METHODS: After screening, this multicenter, randomized, placebo-controlled double-blind trial randomized patients to receive 20 mg sildenafil or placebo 3 times a day (ratio 2:1) for 16 weeks. The primary end point was the reduction in pulmonary vascular resistance. Secondary end points included BODE (body mass index, airflow obstruction, dyspnea, and exercise capacity) index, 6-minute walk test, and quality of life questionnaire. Changes in the partial pressure of arterial oxygen were evaluated as a safety parameter. RESULTS: The final population included 28 patients, 18 in the sildenafil group and 10 in the placebo group. At 16 week, patients treated with sildenafil had a decrease in pulmonary vascular resistance (mean difference with placebo -1.4 WU; 95% confidence interval, ≤ -0.05; p = 0.04). Sildenafil also improved the BODE index, diffusion capacity of the lung for carbon monoxide percentage, and quality of life. Change from baseline in the partial pressure of arterial oxygen was not significantly different between the sildenafil and placebo groups. CONCLUSIONS: This pilot study found that treatment with sildenafil reduced pulmonary vascular resistance and improved the BODE index and quality of life, without a significant effect on gas exchange.

Delayed functional improvement after near-fatal bleeding complication following endobronchial valve therapy for emphysema.

Endoscopic treatment of emphysema is supported by different methods, including valves, coils and sealants. The mechanism is mainly related to volume reduction of targeted area. Endobronchial valves (EBV) appear the most studied method. In a multicentre randomised study, placement of unidirectional endobronchial valves resulted in a statistically significant functional improvement in the treated cohort compared to the control. Adverse events, occurring post procedure, included COPD exacerbations, haemoptysis, pneumothorax and pneumonia. In our centre we treated 30 patients, between January 2009 and February 2012, with variable improvement of lung function and only mild postoperative complications. The case we report here appears very interesting for the unusual near-fatal complication (massive alveolar haemorrage) followed by delayed strong functional improvement (FEV1 +23%; RV -18%; 6MWD:+33%) six months after the valve placement. This improvement could be attributable to the EBV procedure, but an alternative explanation is that the lung volume reduction may have been enhanced by the complication itself, as an effect of alveolar collapse.

Everolimus-based immunosuppressive regimens in lung transplant recipients: impact on CMV infection.

UNLABELLED: Cytomegalovirus (CMV) is one of the most important viral pathogen in solid organ transplant (SOT) recipients, with heart and lung transplant patients being at considerably high risk for CMV direct and indirect effects. Prevention strategies have resulted in significant reduction in disease and CMV related morbidity and mortality. Few studies reported a lower incidence of CMV infections in solid organ transplant recipients treated with immunosuppressive protocols including the mTOR inhibitor everolimus (EVR). PURPOSE: The aim of the current study was to evaluate the impact of EVR-based immunosuppressive regimens on the occurrence and kinetics of CMV infection in a population of lung transplant recipients, at both systemic and pulmonary level. Thirty-two lung transplants (LT) were investigated; eighteen were on EVR-based immunosuppressive regimens. CMV events occurring in the first two years post-transplantation at both systemic and pulmonary levels were reported. PRINCIPAL RESULTS: No differences were reported in CMV viraemia occurrence at both one- and two-year follow up between patients undergoing EVR-based and EVR-free immunosuppressive regimens. Considering CMV episodes at pulmonary levels, as determined by routinely performed broncho-alveolar lavages (BALs), during EVR-administration the patients experienced significantly fewer episodes of high-load CMV (as defined by viral loads⩾10(5) copies/mL) than during EVR-free immunosuppressive regimens. MAJOR CONCLUSION: EVR-based immunosuppressive regimens in lung transplantation settings appear to be associated to lower incidence of clinically relevant CMV episodes at pulmonary levels, striking the possibility of extending the use of EVR to such a group of transplant recipients.

Detection of human cytomegalovirus in transbronchial biopsies from lung transplant recipients.

The role of human cytomegalovirus (HCMV) in lung transplantation (LT) and drawbacks related to viral quantification in bronchoalveolar lavage (BAL) underline the potential usefulness of investigating other specimens. Thirty-three LT recipients were prospectively studied by HCMV quantitative real time PCR on matched transbronchial biopsy (TBB), BAL, and whole blood specimens. Overall, 27/33 patients turned out HCMV-positive in at least one specimen: 7.1 %, 37.1 %, and 13.5 % of TBB, BAL, and blood samples, respectively. No significant association between HCMV on all types of specimens and acute rejection, lymphocytic bronchiolitis, bronchiolitis obliterans and bronchiolitis obliterans syndrome was found. HCMV pneumonia was associated to HCMV detection on TBB (p = 0.003) and whole blood (p = 0.008), not on BAL (p = 0.47). The highest mean viral load was detected in TBB from cases with HCMV pneumonia in comparison to all other cases, suggesting the potential use of HCMV investigation in TBB for evaluating posttransplant complications.

Effect of CMV-immunoglobulins (cytotect biotest) prophylaxis on CMV pneumonia after lung transplantation.

Lung transplant (LT) recipients among solid organ transplant recipients are at high risk for cytomegalovirus (CMV) infections. We evaluated the effect of CMV-Immunoglobulins (CMV-IG) (Cytotect Biotest) on CMV pneumonia diagnosed in 303 follow-up transbronchial biopsies (TBB) of lung transplant recipients. 24 patients (control group, 155 TBB from 1999 to 2002) received acyclovir for 24 months and 33 recipients (study group, 148 TBB from 2003 to 2008) received a combined CMV prophylaxis consisting of CMV-IG (Cytotect Biotest) for 12 months and a short Ganciclovir or Valganciclovir therapy from 21th to 42th postoperative day followed by acyclovir up to 24 months. In our study the percentage of pneumonia at first month TBB was similar in the study group vs the control group, 9.1% (3/33) vs 8.3% (2/24), p=0.9 ns, but after the first month the percentage was significantly lower in the study group in the first year at follow-up TBB, 1% (1/99) vs 6.4% (5/78), p=0.048, and in first two years follow-up TBB, 0.8% (1/122) vs 6.5% 8/124), p=0.018 (STATISTICAL ANALYSIS: Chi-square test for proportion differences). Our data suggest a strong efficacy of CMV-IG prophylaxis in reducing CMV pneumonia after first month in lung transplant recipients.

Does lobectomy for lung cancer in patients with chronic obstructive pulmonary disease affect lung function? A multicenter national study.

OBJECTIVE: The purpose of this study was to evaluate the effect of lobectomy on pulmonary function in patients with chronic obstructive pulmonary disease. METHODS: One hundred thirty-seven patients were analyzed; 49 had normal pulmonary function tests, and 88 had chronic obstructive pulmonary disease. Different functional parameter groups were identified: obstructive (forced expiratory volume in 1 second [FEV1], forced expiratory volume in 1 second/forced vital capacity [FEV1/FVC], and chronic obstructive pulmonary disease index), hyperinflation (residual volume and functional residual capacity), and diffusion (transfer factor of the lung for carbon monoxide). Also, the ratio between observed and predicted postoperative FEV(1) was calculated. RESULTS: In patients with preoperative FEV1 greater than 80% of predicted, postoperative FEV1/FVC slightly but not significantly decreased, and postoperative FEV1 significantly decreased. In patients with preoperative FEV1 less than 65%, postoperative FEV1 and FEV1/FVC significantly increased. In patients with preoperative FEV1/FVC greater than 70%, postoperative FEV1 and FEV1/FVC significantly decreased. In patients with preoperative FEV1/FVC less than 70%, postoperative FEV1/FVC increased, and FEV1 remained unchanged. In patients with a chronic obstructive pulmonary disease index greater than 1.5, postoperative FEV1 and FEV1/FVC significantly decreased, whereas in patients with a chronic obstructive pulmonary disease index less than 1.5, postoperative FEV1/FVC significantly increased and FEV1 remained unchanged. In patients with residual volume and functional residual capacity greater than 115% and transfer factor of the lung for carbon monoxide less than 80% of predicted, postoperative FEV1 diminished less (not significant) compared with patients who had residual volume and functional residual capacity less than 115% (P = .0001). Observed postoperative/predicted postoperative FEV1 was higher if FEV1/FVC was less than 55% (1.46), if FEV1 was less than 80% of predicted (1.21), or if the chronic obstructive pulmonary disease index was less than 1.5 (1.17). CONCLUSIONS: Patients with mild to severe chronic obstructive pulmonary disease could have a better late preservation of pulmonary function after lobectomy than healthy patients.

Mesalamine-induced lung injury in a patient with ulcerative colitis and a confounding autoimmune background: a case report.

Two years after being diagnosed with ulcerative colitis, a 57-year-old man taking oral mesalamine experienced severe respiratory distress due to left lung pleuropneumonitis. Eight months later, severe respiratory distress recurred due to right lung pneumonitis. Extraintestinal manifestations of inflammatory bowel disease or mesalamine-induced pulmonary injury were considered in the differential diagnosis, which was complicated by a history of aseptic meningitis and evidence of an ongoing autoimmune response. The implications of the case are discussed.

Subclinical electrophysiological alterations of phrenic nerve in chronic inflammatory demyelinating polyneuropathy.

Alterations of the phrenic nerve (PN) and pulmonary function tests (PFTs) have been described in patients with chronic inflammatory demyelinating polyneuropathy (CIDP). This study was aimed at assessing the relationship between PN and respiratory function in CIDP patients without clinical signs of respiratory failure. Bilateral PN and right median nerve conduction studies were carried out along with blood gas analysis and PFTs: maximal inspiratory pressure; maximal expiratory pressure; forced vital capacity. The amplitude of the compound muscle action potential of the PN was seen to be altered in 19/24 (79%) patients and latency in 22 (92%). Eighteen patients (75%) showed at least one abnormal PFTs or CO2 partial pressure value. Electrophysiological alterations of the PN were observed in a high percentage of the CIDP patients studied. No statistically significant correlation was observed between PN and PFTs alterations.

Closure of an iatrogenic tracheo-esophageal fistula with bronchoscopic gluing in a mechanically ventilated adult patient.

Management of acquired nonmalignant tracheo-esophageal fistula (TEF) in mechanically ventilated patients is controversial. Surgical correction is often contraindicated because the high operative risk and spontaneous closure is unlikely due to the positive pressure ventilation. We present a case of successful closure of an iatrogenic TEF in a mechanically ventilated patient with bronchoscopic application of fibrin glue. The technique may be proposed in high-risk patients as either an alternative to surgery or as a first-line attempt before surgical correction.