Joseph H. Skalski

The Safety of Cardiopulmonary Exercise Testing in a Population With High-Risk Cardiovascular Diseases

Background—Cardiopulmonary exercise testing (CPX) with measurement of peak oxygen uptake (VO2) is a powerful test for assessment and quantification of functional impairment resulting from cardiovascular disease. The safety of CPX has been established in patients with coronary artery disease and congestive heart failure, but clinical use of CPX in other cardiac diseases has been limited, in part because of a paucity of safety data. This study investigates the safety of CPX in a heterogeneous cohort of patients with a wide variety of underlying high-risk cardiac diagnoses. Methods and Results—This single-center retrospective review examined 5060 CPX studies performed in 4250 unique patients, including 1748 (35%) female subjects and 686 (14%) subjects aged ≥75 years. The primary end point was major adverse event during stress testing. The study population included patients with a variety of high-risk cardiac diseases, including congestive heart failure (n=1289, 25.5%), hypertrophic cardiomyopathy (n=598, 11.8%), pulmonary hypertension (n=194, 3.8%), and aortic stenosis (n=212, 4.2%). This patient population generally had severe functional impairment, including 1192 (24%) patients with peak VO2<14 mL/kg/min. Eight adverse events occurred during CPX, for an adverse event rate of 0.16%. The most common adverse event (n=6) was sustained ventricular tachycardia. There were no fatal events. Conclusions—CPX is generally a safe procedure, even in a population with underlying high-risk cardiovascular diagnoses.

The Use of Indwelling Tunneled Pleural Catheters for Recurrent Pleural Effusions in Patients With Hematologic Malignancies: A Multicenter Study

BACKGROUND Malignant pleural effusion is a common complication of advanced malignancies. Indwelling tunneled pleural catheter (IPC) placement provides effective palliation but can be associated with complications, including infection. In particular, hematologic malignancy and the associated immunosuppressive treatment regimens may increase infectious complications. This study aimed to review outcomes in patients with hematologic malignancy undergoing IPC placement. METHODS A retrospective multicenter study of IPCs placed in patients with hematologic malignancy from January 2009 to December 2013 was performed. Inclusion criteria were recurrent, symptomatic pleural effusion and an underlying diagnosis of hematologic malignancy. Records were reviewed for patient demographics, operative reports, and pathology, cytology, and microbiology reports. RESULTS Ninety-one patients (mean ± SD age, 65.4 ± 15.4 years) were identified from eight institutions. The mean × SD in situ dwell time of all catheters was 89.9 ± 127.1 days (total, 8,160 catheter-days). Seven infectious complications were identified, all of the pleural space. All patients were admitted to the hospital for treatment, with four requiring additional pleural procedures. Two patients died of septic shock related to pleural infection. CONCLUSIONS We present, to our knowledge, the largest study examining clinical outcomes related to IPC placement in patients with hematologic malignancy. An overall 7.7% infection risk and 2.2% mortality were identified, similar to previously reported studies, despite the significant immunosuppression and pancytopenia often present in this population. IPC placement appears to remain a reasonable clinical option for patients with recurrent pleural effusions related to hematologic malignancy.

Pathobiology of Pneumocystis pneumonia: life cycle, cell wall and cell signal transduction.

Pneumocystis is a genus of ascomycetous fungi that are highly morbid pathogens in immunosuppressed humans and other mammals. Pneumocystis cannot easily be propagated in culture, which has greatly hindered understanding of its pathobiology. The Pneumocystis life cycle is intimately associated with its mammalian host lung environment, and life cycle progression is dependent on complex interactions with host alveolar epithelial cells and the extracellular matrix. The Pneumocystis cell wall is a varied and dynamic structure containing a dominant major surface glycoprotein, β-glucans and chitins that are important for evasion of host defenses and stimulation of the host immune system. Understanding of Pneumocystis cell signaling pathways is incomplete, but much has been deduced by comparison of the Pneumocystis genome with homologous genes and proteins in related fungi. In this mini-review, the pathobiology of Pneumocystis is reviewed, with particular focus on the life cycle, cell wall components and cell signal transduction.

Parenchymal cryobiopsies for interstitial lung diseases: A step forward in disease management

The field of interstitial lung diseases (ILDs) has long been regarded as the orphan of respiratory diseases, a perspective primarily driven by a pessimistic, if not nihilistic, therapeutic approach to the prototype, idiopathic pulmonary fibrosis (IPF), which accounts for nearly one third of all ILDs. While unprecedented research efforts have led to substantial improvements in the way respiratory physicians diagnose and prognosticate, IPF remains a fatal disorder for most, with outcomes comparable in many ways to those of lung cancer. A sine qua non criterion for the diagnosis of IPF is the pattern of usual interstitial pneumonia (UIP), a seemingly unfitting term for such a dismal disease, proposed by Dr. Averill Liebow merely because of the high frequency of the histopathologic pattern. Technological advances in multirow highresolution computed tomography (HRCT) imaging, which now allow for full chest scans with a single breath-hold, have admittedly revolutionized the work-up of ILD, often obviating the need for surgical lung biopsies. In parallel to the evolution of imaging, concerted efforts crossing specialty lines have highlighted in recent years the importance of a multidisciplinary approach to the diagnosis of IPF and ILDs in general. Using measures of interobserver agreement as surrogates for diagnostic accuracy, it has become evident that pathology itself is insufficient to establish the diagnosis, which requires a multidisciplinary discussion between pathologists, radiologists and respiratory physicians. In addition, genuine and seemingly justified concerns over complications associated with surgical lung biopsies (SLB) for evaluation of ILD, even in the era of minimally invasive thoracoscopic surgery, have considerably tempered the enthusiasm for histologic sample acquisition. Exacerbations after SLBs in UIP patients are common, and deadly, with a mortality rate approaching 15% in several series. A number of risk factors have been proposed to explain this phenomenon, including stretch injury during single-lung ventilation, oxygen toxicity, ischaemia-reperfusion, fluid overload or even transfusion-related acute lung injury. These developments have led to the common misconception that an accurate histologic diagnosis may not be needed during the work-up of ILD, an approach often justified by physicians based on the lack of efficacious therapeutic strategies for IPF. However, we would suggest that this state of affairs is unacceptable for several reasons. First, histology remains the most important component of the multidisciplinary diagnosis in a majority of cases. In addition, accurate and early diagnosis allows appropriate triaging of patient to transplant referral or clinical trials, informed decision-making process by patients and discontinuation of potentially harmful and ineffective treatment (e.g. corticosteroids or azathioprine in IPF patients). Finally, recently released data from a Food and Drug Administrationmandated study on pirfenidone, an anti-fibrotic molecule already approved in Japan, Europe and Canada, confirm its efficacy in stabilizing IPF, and other agents may become available in the near future. It seems intuitively evident that starting the drug early, before advanced fibrotic changes become obvious on HRCT, could significantly influence the impact of the treatment. Consequently, it will be important to diagnose UIP early in patients with atypical HRCT, present in approximately half of patients with IPF. Conventional bronchoscopic lung biopsies are not generally useful for the diagnosis of IPF and have been described as a ‘step backwards in disease management’. This is primarily due to the fact that the histologic diagnosis of UIP relies on the recognition of a combination of alternating areas of preserved lung architecture and advanced fibrosis, with overall minimal inflammation, the so-called ‘variegated’ appearance of UIP. These features are better appreciated at low magnification, and as such not typically possible with the minute biopsy specimens provided by conventional bronchoscopy biopsy forceps. Cryobiopsies for parenchymal biopsies represent an ingenious use of an old technology to meet these challenges and the technique has been well described. Multiple recent reports haves confirmed the feasibility and safety of this approach in various patient populations including immunosuppressed and ILD patients, lung transplant recipients, and even patient with focal opacities. The volume of the specimens obtained is significantly larger than those obtained by conventional techniques, and the architecture preserved without crush artefact. Bleeding has not been reported with higher frequency, in spite of the impossibility of keeping the scope in wedged position (as both the bronchoscope and cryoprobe need to be removed en bloc), perhaps due to the cold-induced vasoconstriction. The rate of pneumothorax does not appear particularly higher, except in one outlier study, in which the investigators chose to obtain biopsies very close to the pleura bs_bs_banner

Fungal, Viral, and Parasitic Pneumonias Associated with Human Immunodeficiency Virus

Respiratory illness is an important cause of morbidity and mortality in patients with human immunodeficiency virus (HIV). The spectrum of pulmonary disease that can affect patients with HIV is wide and includes opportunistic infection with many fungal, viral, and parasitic organisms. This article reviews the clinical presentation; approach to diagnosis; and management of fungal, viral, and parasitic pneumonias that can develop in patients with HIV including respiratory disease caused by Aspergillus, Cryptococcus, Histoplasma, Coccidioides, Cytomegalovirus, Toxoplasma, and Strongyloides. Because clinical symptoms and radiographic patterns are often insensitive at distinguishing these pulmonary infections, this review particularly focuses on specific host risk factors and diagnostic testing to consider when approaching HIV patients with respiratory illness.

Tunneled Indwelling Pleural Catheters for Refractory Pleural Effusions after Solid Organ Transplant. A Case-Control Study.

RATIONALE The use of tunneled indwelling pleural catheters for management of refractory pleural effusions continues to increase. Pleural space infections are among the most common and serious complication of the procedure. The risk may be higher in patients receiving immunosuppressive medications. OBJECTIVES The aim of this study was to assess the risk of infections complicating placement of a tunneled indwelling pleural catheter in patients who have received a solid organ transplant. METHODS Electronic medical records were retrospectively reviewed to identify patients with prior solid organ transplant who subsequently underwent placement of a tunneled intrapleural catheter. We selected a matched sample of comparison patients without solid organ transplant who underwent the same procedure during the study period. Detailed chart abstraction was performed to compare baseline clinical information with procedure outcomes in both groups. MEASUREMENTS AND MAIN RESULTS Nineteen study patients underwent kidney, liver, lung, or heart transplant. Another 55 patients were included in the nontransplant comparison group. Transplant patients were taking a mean of 2.4 (range, 1-4) immunosuppressive medications. In transplant patients, the intrapleural catheter remained in place for a median of 95 days (interquartile range, 58-256 d). Two of the 19 transplant patients (16.9% 90-day Kaplan-Meier estimate) and 4 of the 55 control patients (11.0% weighted 90-day Kaplan-Meier estimate) developed a major infectious complication (not significant). There were no deaths attributed to intrapleural catheter placement in either group. CONCLUSIONS In a series of 19 patients with solid organ transplantation taking daily immunosuppressive medications who underwent placement of a tunneled intrapleural catheter, we report an 11% rate of major infectious complications over the lifetime of the catheter in the transplant group with no significant difference in 90-day estimated risk of complication between transplant and nontransplant comparison group.

Mycoplasma pneumonia-associated mucositis.

We present a case of a young man with severe mucositis following an upper respiratory tract infection limited to the ophthalmic and oral mucosa while sparing the rest of the skin, genitalia and perianal regions. Investigations revealed that the mucositis was a rare extrapulmonary manifestation of Mycoplasma pneumoniae infection. He had progressive vision-threatening symptoms despite antibiotics and best supportive care and thus was treated with intravenous corticosteroids, immunoglobulins, temporary ocular amniotic membrane grafts and tarsorrhaphy. The patient made an almost complete recovery over 6 weeks.

Expansion of commensal fungus Wallemia mellicola in the gastrointestinal mycobiota enhances the severity of allergic airway disease in mice

The gastrointestinal microbiota influences immune function throughout the body. The gut-lung axis refers to the concept that alterations of gut commensal microorganisms can have a distant effect on immune function in the lung. Overgrowth of intestinal Candida albicans has been previously observed to exacerbate allergic airways disease in mice, but whether subtler changes in intestinal fungal microbiota can affect allergic airways disease is less clear. In this study we have investigated the effects of the population expansion of commensal fungus Wallemia mellicola without overgrowth of the total fungal community. Wallemia spp. are commonly found as a minor component of the commensal gastrointestinal mycobiota in both humans and mice. Mice with an unaltered gut microbiota community resist population expansion when gavaged with W. mellicola; however, transient antibiotic depletion of gut microbiota creates a window of opportunity for expansion of W. mellicola following delivery of live spores to the gastrointestinal tract. This phenomenon is not universal as other commensal fungi (Aspergillus amstelodami, Epicoccum nigrum) do not expand when delivered to mice with antibiotic-depleted microbiota. Mice with Wallemia-expanded gut mycobiota experienced altered pulmonary immune responses to inhaled aeroallergens. Specifically, after induction of allergic airways disease with intratracheal house dust mite (HDM) antigen, mice demonstrated enhanced eosinophilic airway infiltration, airway hyperresponsiveness (AHR) to methacholine challenge, goblet cell hyperplasia, elevated bronchoalveolar lavage IL-5, and enhanced serum HDM IgG1. This phenomenon occurred with no detectable Wallemia in the lung. Targeted amplicon sequencing analysis of the gastrointestinal mycobiota revealed that expansion of W. mellicola in the gut was associated with additional alterations of bacterial and fungal commensal communities. We therefore colonized fungus-free Altered Schaedler Flora (ASF) mice with W. mellicola. ASF mice colonized with W. mellicola experienced enhanced severity of allergic airways disease compared to fungus-free control ASF mice without changes in bacterial community composition.

Health Disparities and Pulmonary Function Testing

Pulmonary function testing (PFTs) is necessary for the diagnosis and optimal management of many common lung diseases. PFTs are underutilized, particularly in the elderly and underprivileged, who face multiple barriers to receiving good medical care, including lack of access to high-quality pulmonary function testing. Language barriers can adversely affect accuracy of PFTs. Many factors including socioeconomic status, air quality, and education all influence lung function. Differences in lung function have been observed by race. Some, but not all, of these observed differences in lung function are attributable to environmental factors. PFT results are interpreted in comparison with reference values derived from large, healthy, mostly white populations. They are calculated using age, gender, height, and race. The use of “race correction” factors to adjust predicted values from reference equations is an imperfect tool that has generated controversy, but is currently the best available methodology. More precise adjustment based on genetic testing may be feasible in the future but is not yet developed for practical use.

Pulmonary Abscess as a Complication of Transbronchial Lung Cryobiopsy.

We present the case of a 49-year-old man who developed pulmonary abscess as a complication of transbronchial lung cryobiopsy. He had been receiving prednisone therapy, but otherwise had no specific risk factors for lung abscess. Cryobiopsy is a novel technique for obtaining peripheral lung parenchymal tissue for the evaluation of diffuse parenchymal lung diseases. Cryobiopsy is being increasingly proposed as an alternative to surgical lung biopsy or conventional bronchoscopic transbronchial forceps biopsy, but the safety profile of the procedure has not been fully appreciated. Pulmonary abscess has been rarely reported as a complication of other bronchoscopic procedures such as endobronchial ultrasound-guided needle biopsy, however, to our knowledge this is the first reported case of pulmonary abscess complicating peripheral lung cryobiopsy.