Imaging aspects of interstitial lung disease in patients with rheumatoid arthritis: Literature review.

OBJECTIVE: Interstitial lung disease (ILD) is a frequent and severe complication of rheumatoid arthritis (RA), resulting in pulmonary fibrosis (PF) and respiratory failure. METHODS: Chest computed tomography (CT-c) or high resolution CT (HRCT) is the main modality for assessment of ILD. We performed a systematic literature review on CT-c/HRCT findings in patients with ILD-RA, using the MEDLINE database for the period from 1991 to 2015. RESULTS: Findings on CT-c/HRCT attributed to ILD-RA are variable (ground glass opacities, reticular and nodular pattern, as well as a combined pattern of emphysema and PF). Correlation of CT-c/HRCT findings with clinical data is inconsistent. CONCLUSIONS: ILD-RA is part of a general autoimmune inflammation and should be integrated into the decision-making process for the treatment of RA. There is an unmet need to design an algorithm which will allow prediction of CT-c changes compatible with ILD-RA with a high probability. Hopefully, this will enable treating patients with ILD-RA early, with possible halting of the progression of ILD-RA toward PF.

Does molecular analysis increase the efficacy of bronchoalveolar lavage in the diagnosis and management of respiratory infections in hemato-oncological patients?

OBJECTIVES: The identification of the specific pathogen responsible for a respiratory infection in patients with hematological malignancies (HM) would ensure relevant treatment and prevent toxicity associated with anti-infective therapy. This large-scale study aimed to explore the clinical impact of fiberoptic bronchoscopy with bronchoalveolar lavage (FOB-BAL) in conjunction with molecular analysis on the diagnosis and management of respiratory infections in hemato-oncological patients. METHODS: All consecutive patients with HM and pulmonary infiltrates, who underwent FOB-BAL between January 2008 and January 2013, were included in the analysis. Clinical characteristics, FOB-BAL results, and treatment adjustments were recorded, and factors predicting a positive BAL were assessed. RESULTS: Four hundred and twenty-five FOB-BAL procedures were analyzed. BAL revealed a specific diagnosis in 219 (51.5%) patients, 208 of them with a pulmonary infection. Infectious etiological agents found were mainly Aspergillus spp (n=142), bacterial species (n=44), and Pneumocystis jirovecii (n=34). Multivariate analysis showed that a lymphoproliferative disease, ≥2 symptoms (dyspnea/cough/hemoptysis/pleuritic pain), and less than 4 days between symptom appearance and FOB-BAL, predicted a positive FOB-BAL result. BAL results prompted a treatment modification in 48% of subjects. CONCLUSIONS: FOB-BAL in conjunction with molecular assays is efficient in the rapid detection of life-threatening infections, allowing for adjustment of anti-infective therapy, which may result in better outcomes and reduce treatment-related toxicity.

Polymicrobial pulmonary infection in patients with hematological malignancies: prevalence, co-pathogens, course and outcome.

PURPOSE: The frequency and clinical significance of polymicrobial pneumonia in patients with hematological malignancies (HM) are poorly understood. The aim of the present study is to describe the prevalence, risk factors, clinical characteristics, and outcome of patients with HM and polymicrobial pneumonia. METHODS: Over a 5 year period, 436 consecutive adult patients with HM and pulmonary infiltrates underwent diagnostic fiberoptic bronchoscopy with bronchoalveolar lavage. For 219 patients an infectious etiology was diagnosed, of them 45 (20.5 %) had polymicrobial etiology. Risk factors, clinical course and outcome of polymicrobial pulmonary infection in patients with HM were established. RESULTS: 45 patients with HM were identified with polymicrobial pulmonary infection, 39 of them with two pathogens, and 6 with three. The most common co-pathogen identified was Aspergillus sp. (87 %). Allogeneic hematopoietic stem cell transplantation (HSCT) and graft versus host disease (GVHD) were predictors of polymicrobial infection. Compared to patients with monomicrobial pneumonia, patients with polymicrobialpulmonary infection had a more severe clinical course with more dyspnea (69 vs. 49 %, P = 0.016), hemoptysis (16 vs. 7 %, P = 0.065) and more required respiratory support (27 vs. 17 %, P = 0.125). In-hospital mortality was significantly higher in patients with polymicrobial pulmonary infection than in patients with monomicrobial pulmonary infection (49 vs. 19 %, P < 0.001). CONCLUSIONS: Polymicrobial pulmonary infection occurs quite frequently in patients with HM, especially in allogeneic HSCT recipients and in patients with GVHD. The clinical course of polymicrobial pulmonary infection is severe and mortality approaches 50 %. The clinician taking care of these patients should always look for additional copathogens in profoundly immunosuppressed patients with pneumonia.

Long-term follow-up of patients with scleroderma interstitial lung disease treated with intravenous cyclophosphamide pulse therapy: a single-center experience.

BACKGROUND: Scleroderma lung disease (ILD-SSc) is treated mainly with cyclophosphamide (CYC). The effectiveness of CYC was judged after 12-24 months in most reports. OBJECTIVES: To analyze the effect of monthly intravenous CYC on pulmonary function tests including forced vital capacity (FVC) and diffusing lung capacity (DLCO), as well as Rodnan skin score (mRSS), during long-term follow-up. METHODS: We retrospectively collected the data on 26 ILD-SSc patients who began CYC treatments before 2007. Changes in FVC, DLCO and mRSS before treatment, and at 1,4 and 7 years after completion of at least six monthly intravenous CYC treatments for ILD-SSc were analyzed. RESULTS: Mean cumulative CYC dose was 8.91 ± 3.25 G. More than 30% reduction in FVC (0%, 8%, and 31% of patients), DLCO (15%, 23%, 31%), and mRSS (31%, 54%, 62%) at years 1, 4 and 7 was registered. During the years 0-4 and 4-7, annual changes in FVC, DLCO and mRSS were 3.2 vs. 0.42% (P < 0.040), 4.6 vs. 0.89% (P < 0.001), and 1.8 vs. 0.2 (P = 0.002). The greatest annual FVC and DLCO reduction over the first 4 years correlated with mortality (P = 0.022). There were no differences in the main variables regarding doses of CYC (< 6 G and > 6 G). CONCLUSIONS: In patients with ILD-SSc, CYC stabilized the reduction of FVC during treatment, but this effect was not persistent. The vascular characteristic of ILD-SSc (DLCO) was not affected by CYC treatment. CYC rapidly improved the mRSS. This effect could be achieved with at least 6 G of CYC. Higher rates of annual reduction in FVC and DLCO in the first 4 years indicate the narrow window of opportunity and raise the question regarding ongoing immunosuppression following CYC infusions.

Lipid profile and statin use: the paradox of survival after acute exacerbation of chronic obstructive pulmonary disease.

BACKGROUND: A paradoxical association between cholesterol level and clinical outcome has been suggested, yet never previously established, in patients with chronic obstructive pulmonary disease (COPD). OBJECTIVES: The authors sought to investigate the interaction between long-term survival, lipid profile and statin use in patients after acute exacerbation of COPD (AECOPD). METHODS: A retrospective study evaluating demographic, clinical and laboratory data of 615 consecutive patients admitted for AECOPD over a mean follow-up period of 24.8 months. Kaplan-Meier survival curves and multivariate analysis were used to identify independent prognostic predictors for all-cause mortality. RESULTS: Mean ± standard deviation (SD) age of the study population was 71.8 ± 11.4 years. Unexpectedly, mean serum cholesterol ± SD levels were significantly higher in survivors (N = 340) versus nonsurvivors (N = 275): 181.5 ± 43.6 versus 171.6 ± 57.2 mg/dL, respectively, (P = 0.0043). Median survival for patients with cholesterol levels <150 and >200 mg/dL were 16.0 and 64.4 months, respectively (P = 0.0173). On multivariate analysis, cholesterol level <150 mg/dL was an independent predictor of mortality, irrespective of cardiovascular risk factors (hazard ratio [HR] = 1.8430, 95% confidence interval [CI] = 1.2547-2.7072, P = 0.0019). Statin use had an independent protective effect, regardless of cholesterol level (HR = 0.4924, 95% CI = 0.2924-0.8292, P = 0.0080). CONCLUSIONS: Low cholesterol levels are significantly associated with increased mortality after AECOPD. Nonetheless, as statin treatment was associated with reduced mortality over the entire range of cholesterol levels, its use should be considered in all COPD patients.

D-dimer as a prognostic biomarker for mortality in chronic obstructive pulmonary disease exacerbation.

BACKGROUND: A major barrier to chronic obstructive pulmonary disease (COPD) research and management is lack of easily obtained biomarkers that are predictive of clinically important outcome measures. OBJECTIVES: We sought to investigate in patients admitted for acute exacerbation of COPD (AECOPD) the association of D-dimer (fibrin degradation product) obtained upon admission with in-hospital mortality and postdischarge prognosis. METHODS: Clinical and laboratory data were evaluated in 61 patients admitted for AECOPD in whom D-dimer levels were obtained and in whom venous thromboembolism/pulmonary embolism was excluded. Receiver operating characteristics curve was used to determine the optimal cutoff level for D-dimer that discriminated survivors versus nonsurvivors during index hospitalization, and during follow-up that extended to a median observation period of 62.6 months. RESULTS: Mean (± SD) age of the study cohort was 71.2 ± 10.5 years. Mean D-dimer level in nonsurvivors (n = 12) was significantly higher than in survivors (n = 49): 3.18 ± 0.97 mg/L versus 1.45 ± 1.18 mg/L, respectively, P = 0.0006. D-dimer level >1.52 mg/L predicted in-hospital mortality with a sensitivity and specificity of 100% and 63.6%, respectively. After discharge, median survival of patients with D-dimer above and below 1.52 mg/L were 9.6 and 62.6 months, respectively (hazard ratio = 2.636; 95% confidence interval = 1.271-6.426, P = 0.0111). CONCLUSIONS: Elevated D-dimer is a reliable prognostic marker for both short-term and long-term survival in patients admitted for AECOPD. Prospective studies are required to further establish the appropriate role of D-dimer as a prognostic biomarker in patients with COPD.

Evaluation of high-sensitivity serum CRP levels compared to markers of airway inflammation and allergy as predictors of methacholine bronchial hyper-responsiveness in children.

BACKGROUND: Bronchial hyper-responsiveness assessed by the methacholine challenge test (MCT) may aid in the diagnosis of asthma, while a negative MCT can help in excluding the diagnosis. Laboratory measures that predict the results of MCT are expected to reduce the number of procedures. We evaluated the capacity of serum high-sensitivity C-reactive protein (hs-CRP) to predict positive or negative MCT in school-aged children and compared it to a marker of airway inflammation, fractional exhaled nitric oxide (FeNO), and markers of allergic sensitization, immune globulin E (IgE) and peripheral blood eosinophils. PATIENTS AND METHODS: Children aged 6-18 years referred for MCT were included in the study. The results of the MCT were compared to hs-CRP levels and FeNO levels, IgE, and peripheral blood eosinophil counts. RESULTS: Of the 131 children assessed, 63 (48 %) patients had positive MCTs (Group I), and 68 (52 %) had negative MCTs (Group II). The best cut-off values to predict a positive MCT by receiver-operating characteristic curves were: 23 ppb for FeNO, 120 IU/mL for IgE, and 500/mL for eosinophils; no cut-off value was found for hs-CRP. The odds ratio for a positive MCT with the above cut-off points were 2.43 (1.05-5.61) for FeNO, 2.4 (1.01-5.74) for IgE, 3.32 (1.13-9.75) for eosinophils, and NS for hs-CRP. No correlation was found between hs-CRP and FeNO, IgE, or eosinophil levels. CONCLUSIONS: hs-CRP levels were not helpful, while FeNO, IgE, and eosinophils were useful in the prediction of methacholine bronchial hyper-responsiveness in our group of children.

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. METHODS: Over a 6-year period, all HIV-negative immunocompromised patients suspected of having an opportunistic pulmonary infection underwent diagnostic bronchoscopy. A multigene PCR assay that detects Pneumocystis jirovecii DNA was used for the diagnosis of PCP. Patients were considered to have PCP if they had underlying immunodeficiency, compatible signs and symptoms, abnormal radiological findings, and Pneumocystis jirovecii DNA was detected in a bronchoalveolar lavage fluid sample. Data was collected retrospectively. RESULTS: PCP was diagnosed in 58 patients. The underlying conditions included haematological malignancies (60.3%), solid tumours (17.2%) and immunosuppressive treatment (22.4%). The most common clinical features in patients with PCP were fever (94.6%), dyspnoea (67.2%) and cough (36.2%). The overall in-hospital mortality was 17.2% (10/58). Mortality was associated with co-infections, high lactate dehydrogenase levels, female gender, and higher pneumonia severity index and acute physiology and chronic health evaluation III scores. CONCLUSIONS: In this study, the mortality of HIV-negative patients with PCP was low compared with previous reports. We hypothesize that this finding resulted from the increased sensitivity of a PCR-based assay, as compared with traditional methods, for the diagnosis of PCP in HIV-negative patients.

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 m(2)). 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.

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.

Preliminary prospective explanatory observation on the impact of 3-month steroid therapy on the objective measures of sleep-disordered breathing.

BACKGROUND: Excess endogenous steroids are a risk factor for obstructive sleep apnea (OSA). The role of exogenous steroids in this setup is not known. In this study, we prospectively looked at the consequences of a 3-month steroid treatment on the objective measures of sleep-disordered breathing. METHODS: Patients scheduled for long-term steroids treatment underwent two sleep studies, the first before initiation and the second after 3 months of steroid therapy. Their weight and neck girth were measured. Correlations between the changes in the body weight, neck girth, and cumulative steroids dose to apnea/hypopnea index (AHI) change were examined. A group of untreated mild OSA patients (n = 23) served as control. RESULTS: Seventeen patients, five males and 12 females, mean age 52.4 ± 12.6 years, were studied. Fifteen patients increased their mean AHI by 56% from 9.8 ± 11.8 to 15.4 ± 15.8, p = 0.004. This increment was significantly higher when compared to the control group. Body weight and neck girth changes and cumulative steroid dose were not correlated to the AHI increment (Spearman's correlation coefficient r = 0.18 and p = 0.49, r = -0.23 and p = 0.37, r = -0.17 and p = 0.51, respectively). CONCLUSIONS: We found that the objective measures of sleep-disordered breathing worsened after the 3-month steroid treatment. Future studies to define pertinent mechanisms and clinical relevance are warranted.

Clinical spectrum and outcome of Nocardia infection: experience of 15-year period from a single tertiary medical center.

INTRODUCTION: Nocardiosis, although very rare, is considered as an important opportunistic infection; however, recent literature is limited. This study describes all cases of nocardial infection treated in the authors' hospital to provide more information about clinical manifestations, species isolated, treatment and outcome of patients with nocardiosis. METHODS: A retrospective review of the clinical features and outcome of nocardial infections was conducted during a 15-year period (1996-2010) at Rambam Health Care Campus. RESULTS: The study included 53 patients with nocardial infection, 43 of them had underlying immunodeficiency. The most common clinical form was pulmonary nocardiosis with and without dissemination (60%), followed by skin and soft tissue infection (21%), bacteremia (11%) and pertonitis (5%). Resistance to trimethoprim/sulfamethoxazile was detected in 15% of isolates; to imipenem in 5% and to ciprofloxacin in 65%. Overall mortality was 25% (13/53), mainly observed in patients with pulmonary involvement (37.5%). CONCLUSIONS: Nocardiosis is a rare infection and mainly affects immunocompromised patients. Higher index of suspicion is needed for earlier diagnosis and treatment to improve prognosis.

Pulmonary arteries involvement in Takayasu's arteritis: two cases and literature review.

OBJECTIVES: To review pulmonary arteritis (PA) complicated by pulmonary arterial hypertension (PAH) in Takayasu's arteritis (TA). METHODS: Two cases of PA and PAH in TA patients and similar cases published in the Medline database from 1975 to 2009 were reviewed. RESULTS: Forty-six cases (females 89.1%, Asians 65%, mean age 34.6 years) were analyzed, 42.2% of which had PAH. Isolated PA was reported in 31.8%. Respiratory symptoms were presented as dyspnea (75.5%), chest pain (48.9%), hemoptysis (42.2%), and cough (17.7%). Hypertension, vascular bruits, and diminished/absent pulses were reported in 48.9% of patients. A diagnosis of PA was based on abnormal uptake on pulmonary perfusion scan and a finding of stenosis, narrowing, occlusion, and irregularity on computed tomography or magnetic resonance imaging, and/or pulmonary angiography. Patients were treated with glucocorticoids (77.5%), disease-modified antirheumatic drugs (35%), and warfarin (20%); only a few were treated with biological agents. Vascular procedures were performed in 52.5% of cases, on pulmonary arteries in 37.5% with good results. The outcome was death in 20.5% of PA patient and 33.3% in PAH patients. CONCLUSIONS: TA may be complicated by life-threatening PA and PAH. Clinical signs are not specific and may be masked by involvement of the aorta and its branches. Treatment with glucocorticoids and disease-modified antirheumatic drugs has only partial effect, which may be intensified by biological agents. Invasive procedures on pulmonary arteries may be a complementary option. PA and PAH in TA patients should be recognized early and treated promptly for prevention of irreversible vascular damage.

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.

Idiopathic pulmonary arterial hypertension or chronic thromboembolic pulmonary hypertension: can we be certain?

Idiopathic pulmonary arterial hypertension (IPAH) is an isolated small-vessel disease comprising vasoconstriction, remodeling and thrombosis of small pulmonary arteries. However, there is evidence that IPAH does not respect anatomic boundaries and might extend into large vessels such as large central thrombi. On the other hand, chronic thromboembolic pulmonary hypertension (CTEPH) represents a distinct category of pulmonary hypertension as it is thought to be due to an occlusion of the major pulmonary arteries following a thromboembolic event. However, it is currently evident that in most patients there is a concomitant small-vessel disease. The involvement of both small and large vessels in both IPAH and CTEPH, together with a high incidence of silent thromboembolic events, might create difficulties in identifying the true cause of pulmonary hypertension. An accurate diagnosis of the cause determines the management and prognosis. Patients with CTEPH can potentially be offered curative surgery in the form of pulmonary endarterectomy; however, oxygen, vasodilators, anticoagulation, and lung transplantation are more feasible options for IPAH.

Obstructive uropathy caused by retroperitoneal fibrosis presents as a late manifestation of sarcoidosis.

Obstructive uropathy in sarcoidosis can result from retroperitoneal involvement, retroperitoneal fibrosis (RPF), renal stones, or ureteral involvement. We report acute kidney injury (AKI) from obstructive uropathy because of RPF in a female patient, 2 years following the resolution of pulmonary sarcoidosis. We propose that RPF may occur in sarcoidosis even when a lag of years separates the presentations of the illnesses.

Validation of an ambulatory cough detection and counting application using voluntary cough under different conditions.

BACKGROUND: While cough is an important defence mechanism of the respiratory system, its chronic presence is bothersome and may indicate the presence of a serious disease. We hereby describe the validation process of a novel cough detection and counting technology (PulmoTrack-CC, KarmelSonix, Haifa, Israel). METHODS: Tracheal and chest wall sounds, ambient sounds and chest motion were digitally recorded, using the PulmoTrack(R) hardware, from healthy volunteers coughing voluntarily while (a) laying supine, (b) sitting, (c) sitting with strong ambient noise, (d) walking, and (e) climbing stairs, a total of 25 minutes per subject. The cough monitoring algorithm was applied to the recorded data to detect and count coughs.The detection algorithm first searches for cough 'candidates' by identifying loud sounds with a cough pattern, followed by a secondary verification process based on detection of specific characteristics of cough. The recorded data were independently and blindly evaluated by trained experts who listened to the sounds and visually reviewed them on a sonogram display.The validation process was based on two methods: (i) Referring to an expert consensus as gold standard, and comparing each cough detected by the algorithm to the expert marking, we marked True and False, positive and negative detections.These values were used to evaluate the specificity and sensitivity of the cough monitoring system. (ii) Counting the number of coughs in longer segments (t = 60 sec, n = 300) and plotting the cough count vs. the corresponding experts' count whereby the linear regression equation, the regression coefficient (R2) and the joint-distribution density Bland-Altman plots could be determined. RESULTS: Data were recorded from 12 volunteers undergoing the complete protocol. The overall Specificity for cough events was 94% and the Sensitivity was 96%, with similar values found for all conditions, except for the stair climbing stage where the Specificity was 87% with Sensitivity of 97%. The regression equation between the PulmoTrack-CC cough event counts and the Experts' determination was with R2 of 0.94. DISCUSSION: This validation scheme provides an objective and quantitative assessment method of a cough counting algorithm in a range of realistic situations that simulate ambulatory monitoring of cough. The ability to detect voluntary coughs under acoustically challenging ambient conditions may represent a useful step towards a clinically applicable automatic cough detector.

Radiological features of Pneumocystis jirovecii Pneumonia in immunocompromised patients with and without AIDS.

The aim of this study was to compare chest computerized tomography (CT) findings of Pneumocystis jirovecii pneumonia (PCP) in immunocompromised patients with and without acquired immune deficiency syndrome (AIDS). Chest CT findings and clinical parameters of 38 consecutive immunocompromised patients, nine with AIDS and 29 with other causes of immunosuppression, were characterized and compared. PCP in patients without AIDS was diagnosed after a significantly shorter time interval from symptom onset: 8 +/- 6 vs. 18 +/- 1.0 days (p = 0.024). From a radiographic point of view, non-AIDS patients had a significantly higher proportion of diffuse ground glass lesions, 86 vs. 44% (p = 0.02), and a lower proportion of cystic lesions, 3 vs. 56% (p = 0.015). The two subgroups did not differ in smoking status and the number of pack-years. On multivariant analysis, only the presence of AIDS was found to be a risk factor for the formation of pulmonary cystic lesions. Different immune reactions to the parasite P. jirovecii in immunocompromised patients with and without AIDS results in a different time lag between symptoms and a correspondingly different radiographic pattern: widespread ground glass opacities in the former and cystic lesions in the latter.

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.