Emilia Hardak

The Increased Risk for Pneumocystis Pneumonia in Patients Receiving Rituximab-CHOP-14 Can Be Prevented by the Administration of Trimethoprim/Sulfamethoxazole: A Single-Center Experience

Recent studies suggest an increased risk for Pneumocystis jirovecii pneumonia (PJP) in adults receiving short-interval rituximab-CHOP (cyclophosphamide, doxorubicin, vincristine and prednisone) therapy for diffuse large cell B cell lymphoma (DLBCL). This retrospective study evaluates precise PJP incidence and the efficacy of anti-PJP prophylaxis in DLBCL. Patients with DLBCL, aged ≧18 years and treated between December 2004 and December 2010, were included. Details of treatment-related respiratory infections, focusing on PJP incidence, risk factors and prophylaxis, were assessed. A total of 132 patients were analyzed; 47 were treated with rituximab-CHOP therapy every 21 days (R-CHOP-21) and 85 were treated every 14 days (R-CHOP-14). The incidence of treatment-related respiratory infections was higher in patients receiving R-CHOP-14. PJP was diagnosed in 5 patients: 4 in the R-CHOP-14 (6.6%) and 1 in the R-CHOP-21 cohort (2.6%), using triplex polymerase chain reaction (PCR) for PJ in bronchoalveolar fluid. None of the patients receiving P.jirovecii prophylaxis (n = 33) developed PJP, compared with 6.6% of those treated with R-CHOP-14 without such prophylaxis. An older age and R-CHOP administered every 14 rather than every 21 days increased the PJP risk. Trimethoprim/sulfamethoxazole prophylaxis is found to be highly efficient in preventing this life-threatening complication and, therefore, should be recommended for patients receiving the R-CHOP-14 regimen.

Impact of PCR-based diagnosis of invasive pulmonary aspergillosis on clinical outcome

The mortality rate of 60–90% in invasive pulmonary aspergillosis (IPA) is partly explained by diagnostic delay due to the limitation of current diagnostic tests. We assessed the influence of Aspergillus species (ASP) DNA detection by PCR from bronchoalveolar lavage (BAL) fluid, a new tool for diagnosing IPA, on the outcome of this disease in immune-compromised patients. The study population comprised 107 consecutive patients with hematological malignancies from a single medical center with IPA diagnosed between 1998 and 2005. Clinical variables and mortality rates were compared between two groups diagnosed according to traditional criteria without and with PCR-based ASP DNA detection in BAL fluid. The overall mortality rate during the study period was 38.3%. The addition of PCR to the diagnostic criteria shifted 31 patients from possible to probable IPA. Patients diagnosed with probable IPA according to traditional microbiological methods had significantly higher mortality rates compared to their counterparts who had in addition a PCR-based diagnosis (80 vs 35.6%, P=0.003). This study demonstrates that PCR-based ASP DNA detection for a diagnosis of IPA from BAL fluid has a significant effect on the outcome of patients with IPA, probably related to earlier diagnosis.

Polymerase chain reaction-based detection of Pneumocystis jirovecii in bronchoalveolar lavage fluid for the diagnosis of pneumocystis pneumonia.

Introduction:The diagnosis of pneumocystis pneumonia (PCP) in non-human immunodeficiency virus (HIV)-infected immunocompromised patients is notoriously difficult. The recent advent of polymerase chain reaction (PCR)-based detection systems, based on the identification of single fungal genes, has markedly improved diagnostic accuracy in this ominous disease. In an attempt to further improve diagnostic yield, the authors used a PCR-based detection system for Pneumocystis jirovecii, based on targeting 3 distinct genes. Methods:During the 4-year period (January 2005 to January 2009), all consecutive immunocompromised patients suspected of having PCP in the differential diagnosis underwent bronchoscopy with bronchoalveolar lavage sampling for the evaluation of the etiology of pulmonary infiltrates. Bronchoalveolar fluid was tested for the presence of a wide variety of possible etiological microorganisms. Results:In a cohort of 214 immunocompromised patients (of which 198 were non-HIV immunocompromised patients) who underwent bronchoscopy with bronchoalveolar lavage for evaluation of pulmonary infiltrates, PCR correctly diagnosed PCP in 75% (42/56) compared with 14% (8/56) diagnosed by traditional stains, and increased diagnostic yield 5.4-fold. Conclusions:Given the absence of a sensitive gold standard, this study demonstrates the usefulness of a multigene PCR-based detection of Pneumocystis jirovecii DNA for supporting the clinical diagnosis of PCP, with high sensitivity and negative predictive value rates compared with direct stains, especially in non-HIV immunocompromised patients.

Outcome of Pneumocystis jirovecii pneumonia diagnosed by polymerase chain reaction in patients without human immunodeficiency virus infection

Background and objective:  Pneumonia caused by Pneumocystis jirovecii (PCP) in patients without human immunodeficiency virus (HIV) infection is associated with high mortality. The diagnosis of PCP at our institution is based on detection of DNA using a polymerase chain reaction (PCR) assay. The aim of this study was to describe the clinical manifestations, outcomes and factors associated with mortality due to PCP, as diagnosed by PCR, in patients without HIV infection.

Radiological findings of early invasive pulmonary aspergillosis in immune‐compromised patients

Data on the radiological features of invasive pulmonary aspergillosis (IPA) in early stages is scanty. Detection of Aspergillus (ASP) species in broncho‐alveolar (BAL) fluid by polymerase chain reaction (PCR) enables early diagnosis of IPA. This study describes the radiological features of early stages of IPA. Chest computerized tomography (CT) films of 22 consecutive immune‐compromised patients with IPA diagnosed with the aid of ASP PCR testing from BAL fluid were characterized and compared to that of 18 similar patients diagnosed with traditional bacteriological methods and to data from the literature. It was found that patients diagnosed with the aid of ASP PCR testing tended to have focal disease as manifested by more 11–30 mm nodules with halo (68% vs. 33%, p = 0.04), more focal ground glass (single area 32% vs. 6%, p = 0.05, patchy 32% vs. 0%, p = 0.01) and less diffuse ground glass (0% vs. 22%, p = 0.03), less cavitations (5% vs. 28%, p = 0.05) and less consolidations (segmental 14% vs. 50%, p = 0.02 and diffuse 14% vs. 67%, p = 0.001). It was concluded that the radiological appearance of early IPA diagnosed with the aid of PCR testing included mainly discrete small nodules with halo and focal ground glass, representing the early stage of the disease. Copyright

Characterization of Pulmonary Venous Hypertension Patients with Reactive Pulmonary Hypertension as Compared to Proportional Pulmonary Hypertension

Background: Patients with pulmonary venous hypertension (PVH) secondary to left heart disease can be further classified according to their hemodynamic profile: pulmonary hypertension (PH) in proportion to the pulmonary capillary wedge pressure (PCWP) and PH out of proportion to the PCWP or reactive PH. Currently, there are no measures that enable prediction of the development of reactive PH in patients with left heart disease. Objectives: In this study, we aim to characterize PVH patients with reactive PH as compared to proportional PH in an attempt to create a distinct profile for patients with left heart disease carrying a high risk for the development of reactive PH. Methods: Thirty-three PVH patients with reactive PH and 29 PVH patients with proportional PH were analyzed retrospectively over a 6-year period. Clinical, laboratory, echocardiographic and hemodynamic parameters were noted and compared between subgroups. Results: There was no significant difference between PVH patients with reactive and proportional PH with regard to gender, age (65.91 ± 11.9 vs. 66.69 ± 10.5 years) and body surface area (1.89 ± 0.24 vs. 1.9 ± 0.23 m2). Prevalence of the metabolic syndrome components was similar in both groups. Interestingly, PCWP was similar in both groups, as were the structural and functional parameters of the left heart. Conclusions: PVH patients with reactive PH have a similar profile as patients with proportional PH; consequently, the evolution of reactive PH is unpredictable. Therefore, it is imperative that physicians maintain a high index of suspicion for the development of reactive PH even in the early stage of heart disease.

Nitrofurantoin pulmonary toxicity: neglected threat.

Nitrofurantoin lung toxicity was diagnosed among ten patients receiving 50 mg/day to prevent recurrent urinary tract infection. In six patients a symptomatic period of 3-36 months preceded the diagnosis. All but one patient, with irreversible lung injury at presentation recovered completely, five after drug discontinuation and four after steroids therapy. Large amount of data regarding unexpected, sometimes severe pulmonary toxicity during nitrofurantoin therapy should maintain a high index of suspicion for the drug usage among patients with non-resolving pulmonary symptoms. Alternatively, the use of other anti-microbial agents with a better risk-to-benefit ratio should be considered.

The Response to Bronchodilators in Adults is not Predictive of Bronchial-hyperreactivity

Background. In some subjects with suspected asthma who have normal spirometry, administration of bronchodilators (BD) improves expiratory flow rates. The predictive value of this phenomenon in adults is not known. Objectives. To evaluate the predictive value of the response to BD for bronchial hyper-responsiveness (BHR) using the metacholine challenge test (MCT). Patients and methods. The study population included 62 non-smoking adult patients (41.9% women) 29.5 ± 15.5 years of age (range 18–64 years) with suspected asthma with normal spirometry that underwent MCT within 1 week. The response to BD (200 μ g inhaled salbutamol) was compared between subjects with positive and negative MCT using cutoff levels of provocative concentrations of metacholine causing a 20% decrease in forced expiratory volume in 1 second (FEV1) (PC20) of 4 and 8 mg/mL. Results. Mean (± SD) baseline FEV1 was 87.8 ± 12% of predicted. After BD administration the mean FEV1 increased by 4.3 ± 3.9%. The prevalence of BHR was 17.7% and 25.8% for PC20 for PC20 of 4 mg/mL and 8 mg/mL, respectively. The post-BD FEV1 increment for subjects with positive and negative MCT tests was 3.9% ± 3.3% versus 4.4% ± 4.1%, respectively; p = 0.89, using cutoff of 4 mg/mL. The corresponding figures for cutoff of 8 mg/ml were 4.3% ± 3.1% vs. 4.3% ± 4.2%, respectively; p = 0.8465. There was no correlation between post-BD FEV1 increment and PC20 values in patients with positive MCT test for the above-mentioned cutoff levels (correlation coefficient r = 0.1645, p = 0.6289; and r = 0.2417, p = 0.4051, respectively). Conclusions. In adults with suspected asthma who have normal spirometry, the response to BD cannot be used to predict BHR.

Reply 1: Correspondence

and fewer Pneumocystis organisms. Therefore, a consolidation-predominant pattern should not preclude a suspicion of PJP. Early diagnosis of PJP usually relies on a high index of suspicion. In non-HIVinfected patients, transplantation and corticosteroid use are two important risk factors. A susceptible host with risk factors presenting with atypical pneumonia should elicit a suspicion of this disease regardless of typical chest imaging presented. Furthermore, the imaging pattern of PJP varies with HIV-infected status and disease stage. Evolutionary changes may occur after treatment. In this presented case, the subpleural lesions changed from consolidation to GGO with crazy-paving pattern after 2 weeks of treatment (Fig. 1d). Nevertheless, initial GGO lesions may progress to alveolar consolidation in few days, if no definite treatment is provided. In conclusion, PJP in non-HIV-infected patients has different clinical and radiographical presentations from that in HIV-infected patients. The clinical and radiographical features from HIV-infected patients cannot be totally applied to diagnose PJP in non-HIVinfected patients.

Contents Vol. 83, 2012

433 Joint Annual Meeting of the Swiss Society of Pneumology Swiss Society of Pediatric Pneumology Swiss Society for Thoracic Surgery Swiss Underwater and Hyperbaric Medical Society Crans-Montana, April 25–27, 2012 479 Congress Calendar