Early postoperative management after lung transplantation: Results of an international survey.

INTRODUCTION: Little data exist regarding optimal therapeutic strategies postoperatively after lung transplant (LTx). Current practice patterns rely on expert opinion and institutional experience resulting in nonuniform postoperative care. To better define current practice patterns, an international survey of LTx clinicians was conducted. METHODS: A 30-question survey was sent to transplant clinicians via email to the International Society of Heart and Lung Transplantation open forum mailing list and directly to the chief transplant surgeon and pulmonologist of all LTx centers in the United States. RESULTS: Fifty-two clinicians representing 10 countries responded to the survey. Sedatives use patterns included: opiates + propofol (57.2%), opiates + dexmedetomidine (18.4%), opiates + intermittent benzodiazepines (14.3%), opiates + continuous benzodiazepines (8.2%), and opiates alone (2%). About 40.4% reported no formal sedation scale was followed and 13.5% of programs had no formal policy on sedation and analgesia. A lung protective strategy was commonly employed, with 13.8%, 51.3%, and 35.9% of respondents using tidal volumes of <6 mL/kg ideal body weight (IBW), 6 mL/kg IBW, and 8 mL/kg IBW, respectively. CONCLUSION: Practice patterns in the early postoperative care of lung transplant recipients differ considerably among centers. Many of the reported practices do not conform to consensus guidelines on management of critically ill patients.

Diarrhea-An uncommon presentation of tertiary adrenal insufficiency following heart transplantation.

Diarrhea following organ transplantation is usually associated with infection and immunosuppression therapy. We describe two patients with diarrhea following orthotopic heart transplantation due to tertiary adrenal insufficiency.

Increased resource use in lung transplant admissions in the lung allocation score era.

RATIONALE: In 2005, the lung allocation score (LAS) was implemented to prioritize organ allocation to minimize waiting-list mortality and maximize 1-year survival. It resulted in transplantation of older and sicker patients without changing 1-year survival. Its effect on resource use is unknown. OBJECTIVES: To determine changes in resource use over time in lung transplant admissions. METHODS: Solid organ transplant recipients were identified within the Nationwide Inpatient Sample (NIS) data from 2000 to 2011. Joinpoint regression methodology was performed to identify a time point of change in mean total hospital charges among lung transplant and other solid-organ transplant recipients. Two temporal lung transplant recipient cohorts identified by joinpoint regression were compared for baseline characteristics and resource use, including total charges for index hospitalization, charges per day, length of stay, discharge disposition, tracheostomy, and need for extracorporeal membrane oxygenation. MEASUREMENTS AND MAIN RESULTS: A significant point of increased total hospital charges occurred for lung transplant recipients in 2005, corresponding to LAS implementation, which was not seen in other solid-organ transplant recipients. Total transplant hospital charges increased by 40% in the post-LAS cohort ($569,942 [$53,229] vs. $407,489 [$28,360]) along with an increased median length of stay, daily charges, and discharge disposition other than to home. Post-LAS recipients also had higher post-transplant use of extracorporeal membrane oxygenation (odds ratio, 2.35; 95% confidence interval, 1.56-3.55) and higher incidence of tracheostomy (odds ratio, 1.52; 95% confidence interval, 1.22-1.89). CONCLUSIONS: LAS implementation is associated with a significant increase in resource use during index hospitalization for lung transplant.

Clarithromycin for prevention of bronchiolitis obliterans syndrome in lung allograft recipients.

BACKGROUND: Bronchiolitis obliterans syndrome (BOS) is the major limitation to long-term survival following lung transplantation and strategies to reduce its incidence have remained elusive. Macrolides may stabilize lung function in patients with established BOS. Their role, however, in prevention of BOS remains unexamined. METHODS: Survival and BOS-free survival of 102 lung allograft recipients (LARs), transplanted at a single center between July 1995 and December 2001 who routinely received clarithromycin, were compared with two different control groups. The first control group consisted of 44 LARs from the same center who were transplanted from January 2002 onwards and did not receive clarithromycin. The second control group consisted of a contemporaneous cohort of 5089 recipients, transplanted between 1995 and 2001, reported to the United Network for Organ Sharing database. RESULTS: When compared with the first control group, BOS-free survival was reduced in LARs receiving clarithromycin. Univariate (hazard ratio [HR] 3.13, p-value = 0.004) and multivariate (HR 3.49, p-value = 0.04) analyses showed that routine use of clarithromycin was associated with an increased risk of developing BOS. When compared with the second control group, the five-yr survival of clarithromycin group was similar (p-value = 0.24). CONCLUSIONS: Routine use of clarithromycin does not delay development of BOS or improve survival.

Comparison of sirolimus with azathioprine in a tacrolimus-based immunosuppressive regimen in lung transplantation.

RATIONALE: Lung transplantation has evolved into a life-saving therapy for select patients with end-stage lung diseases. However, long-term survival remains limited because of chronic rejection. Sirolimus is beneficial in preventing cardiac rejection and may decrease rejection after lung transplantation. OBJECTIVES: To determine the potential benefit versus risk of sirolimus in lung transplantation. METHODS: We conducted a multicenter randomized, open label controlled trial comparing sirolimus (SIR) with azathioprine (AZA) in a tacrolimus-based immunosuppressive regimen in lung transplantation. The primary end point was the incidence of acute rejection at 1 year after transplantation between the two study groups. MEASUREMENTS AND MAIN RESULTS: One hundred eighty-one patients were randomized to be included in this study. At 1 year after transplantation, there was no significant difference in the incidence of grade A acute rejection between the two study groups. Similarly, the incidence of chronic rejection and graft survival was no different between the two study groups. Cytomegalovirus infection was decreased in the SIR arm compared with the AZA arm (relative risk, 0.67 [95% confidence interval, 0.55, 0.82]; P < 0.01). There was a higher rate of adverse events leading to early discontinuation of SIR (64%) compared with AZA (49%) during the course of this study. CONCLUSIONS: Sirolimus, an mTOR inhibitor, did not decrease the incidence of acute rejection at 1 year compared with azathioprine in lung transplantation. These results differ from previous results in cardiac and renal transplantation and emphasize the need for multicenter randomized controlled trials in lung transplantation. Clinical trial registered with www.clinicaltrials.gov (NCT 00321906).

Mucous solids and liquid secretion by airways: studies with normal pig, cystic fibrosis human, and non-cystic fibrosis human bronchi.

To better understand how airways produce thick airway mucus, nonvolatile solids were measured in liquid secreted by bronchi from normal pig, cystic fibrosis (CF) human, and non-CF human lungs. Bronchi were exposed to various secretagogues and anion secretion inhibitors to induce a range of liquid volume secretion rates. In all three groups, the relationship of solids concentration (percent nonvolatile solids) to liquid volume secretion rate was curvilinear, with higher solids concentration associated with lower rates of liquid volume secretion. In contrast, the secretion rates of solids mass and water mass as functions of liquid volume secretion rates exhibited positive linear correlations. The y-intercepts of the solids mass-liquid volume secretion relationships for all three groups were positive, thus accounting for the higher solids concentrations in airway liquid at low rates of secretion. Predictive models derived from the solids mass and water mass linear equations fit the experimental percent solids data for the three groups. The ratio of solids mass secretion to liquid volume secretion was 5.2 and 2.4 times higher for CF bronchi than for pig and non-CF bronchi, respectively. These results indicate that normal pig, non-CF human, and CF human bronchi produce a high-percent-solids mucus (>8%) at low rates of liquid volume secretion (≤1.0 µl·cm(-2)·h(-1)). However, CF bronchi produce mucus with twice the percent solids (~8%) of pig or non-CF human bronchi at liquid volume secretion rates ≥4.0 µl·cm(-2)·h(-1).

Extended valganciclovir prophylaxis to prevent cytomegalovirus after lung transplantation: a randomized, controlled trial.

BACKGROUND: Cytomegalovirus (CMV) is the most prevalent opportunistic infection after lung transplantation. Current strategies do not prevent CMV in most at-risk patients. OBJECTIVE: To determine whether extending prophylaxis with oral valganciclovir from the standard 3 months to 12 months after lung transplantation is efficacious. DESIGN: Randomized, clinical trial. Patients were randomly assigned by a central automated system to treatment or placebo. Patients and investigators were blinded to treatment status. (ClinicalTrials.gov registration number: NCT00227370) SETTING: Multicenter trial involving 11 U.S. lung transplant centers. PATIENTS: 136 lung transplant recipients who completed 3 months of valganciclovir prophylaxis. INTERVENTION: 9 additional months of oral valganciclovir (n = 70) or placebo (n = 66). MEASUREMENTS: The primary end point was freedom from CMV disease (syndrome or tissue-invasive) on an intention-to-treat basis 300 days after randomization. Secondary end points were CMV disease severity, CMV infection, acute rejection, opportunistic infections, ganciclovir resistance, and safety. RESULTS: CMV disease occurred in 32% of the short-course group versus 4% of the extended-course group (P < 0.001). Significant reductions were observed with CMV infection (64% vs. 10%; P < 0.001) and disease severity (110 000 vs. 3200 copies/mL, P = 0.009) with extended treatment. Rates of acute rejection, opportunistic infections, adverse events, CMV UL97 ganciclovir-resistance mutations, and laboratory abnormalities were similar between groups. During the 6 months after study completion, a low incidence of CMV disease was observed in both groups. LIMITATION: Longer-term effects of extended prophylaxis were not assessed. CONCLUSION: In adult lung transplant recipients who have received 3 months of valganciclovir, extending prophylaxis by an additional 9 months significantly reduces CMV infection, disease, and disease severity without increased ganciclovir resistance or toxicity. A beneficial effect with regard to prevention of CMV disease seems to extend at least through 18 months after transplantation.

Understanding the andromeda strain - The role of cytokine release, coagulopathy and antithrombin III in SARS-CoV2 critical illness.

As the current coronavirus pandemic continues and cases of COVID-19 critical illness rise, physicians and scientists across the globe are working to understand and study its pathophysiology. Part of the pathology of this illness may result from its prothrombotic potential as witnessed from derangements in coagulation and thrombotic complications reported in observational studies performed in China and Europe to findings of microthrombosis upon autopsy analysis of patients who succumbed to COVID-19. Multiple organizations, including the American Society of Hematology (ASH), recommend the routine use of prophylactic heparin to temper the thrombotic complications of this illness given its mortality benefit in severe COVID-19 infections. Reductions in circulating levels of Antithrombin III (AT), the primary mediator of heparin's action, is present in cases of coronavirus related critical illness. AT's use as a prognostic marker, an important effector of heparin resistance, and a potential therapeutic target for COVID-19 remains to be explored.

Correlates of survival after autoantibody reduction therapy for acute IPF exacerbations.

BACKGROUND: No medical treatment has proven efficacy for acute exacerbations of idiopathic pulmonary fibrosis (AE-IPF), and this syndrome has a very high mortality. Based on data indicating humoral autoimmune processes are involved in IPF pathogenesis, we treated AE-IPF patients with an autoantibody reduction regimen of therapeutic plasma exchange, rituximab, and intravenous immunoglobulin. This study aimed to identify clinical and autoantibody determinants associated with survival after autoantibody reduction in AE-IPF. METHODS: Twenty-four(24) AE-IPF patients received the autoantibody reduction regimen. Plasma anti-epithelial autoantibody titers were determined by HEp-2 indirect immunofluorescence assays in 22 patients. RESULTS: Mean age of the patients was 70 + 7 years old, and 70% were male. Beneficial clinical responses that occurred early during therapy were a favorable prognostic indicator: supplemental O2 flows needed to maintain resting SaO2>92% significantly decreased and/or walk distances increased among all 10 patients who survived for at least one year. Plasma anti-HEp-2 autoantibody titers were ~-three-fold greater in survivors compared to non-survivors (p<0.02). Anti-HEp-2 titers >1:160 were present in 75% of the evaluable one-year survivors, compared to 29% of non-survivors, and 10 of 12 patients (83%) with anti-HEP-2 titers <1:160 died during the observation period (Hazard Ratio = 3.3, 95% Confidence Interval = 1.02-10.6, p = 0.047). CONCLUSIONS: Autoantibody reduction therapy is associated with rapid reduction of supplemental oxygen requirements and/or improved ability to ambulate in many AE-IPF patients. Facile anti-epithelial autoantibody assays may help identify those most likely to benefit from these treatments.

The role of chloride anion and CFTR in killing of Pseudomonas aeruginosa by normal and CF neutrophils.

Chloride anion is essential for myeloperoxidase (MPO) to produce hypochlorous acid (HOCl) in polymorphonuclear neutrophils (PMNs). To define whether chloride availability to PMNs affects their HOCl production and microbicidal capacity, we examined how extracellular chloride concentration affects killing of Pseudomonas aeruginosa (PsA) by normal neutrophils. PMN-mediated bacterial killing was strongly dependent on extracellular chloride concentration. Neutrophils in a chloride-deficient medium killed PsA poorly. However, as the chloride level was raised, the killing efficiency increased in a dose-dependent manner. By using specific inhibitors to selectively block NADPH oxidase, MPO, and cystic fibrosis transmembrane conductance regulator (CFTR) functions, neutrophil-mediated killing of PsA could be attributed to three distinct mechanisms: CFTR-dependent and oxidant-dependent; chloride-dependent but not CFTR- and oxidant-dependent; and independent of any of the tested factors. Therefore, chloride anion is involved in oxidant- and nonoxidant-mediated bacterial killing. We previously reported that neutrophils from CF patients are defective in chlorination of ingested bacteria, suggesting that the chloride channel defect might impair the MPO-hydrogen peroxide-chloride microbicidal function. Here, we compared the competence of killing PsA by neutrophils from normal donors and CF patients. The data demonstrate that the killing rate by CF neutrophils was significantly lower than that by normal neutrophils. CF neutrophils in a chloride-deficient environment had only one-third of the bactericidal capacity of normal neutrophils in a physiological chloride environment. These results suggest that CFTR-dependent chloride anion transport contributes significantly to killing PsA by normal neutrophils and when defective as in CF, may compromise the ability to clear PsA.

CD28 down-regulation on CD4 T cells is a marker for graft dysfunction in lung transplant recipients.

RATIONALE: Repeated antigen-driven proliferations cause CD28 on T cells to down-regulate. We hypothesized that alloantigen-induced proliferations could cause CD28 down-regulation in lung transplant recipients. OBJECTIVES: To ascertain if CD28 down-regulation on CD4 T cells associated with manifestations of allograft dysfunction in lung transplant recipients. METHODS: Peripheral blood CD4 T cells from 65 recipients were analyzed by flow cytometry, cytokine multiplex and proliferative assays, and correlated with clinical events. MEASUREMENTS AND MAIN RESULTS: Findings that CD28 was present on less than 90% of total CD4 T cells were predominantly seen among the recipients with bronchiolitis obliterans syndrome (specificity = 88%). Perforin and granzyme B were produced by >50% of the CD4(+)CD28(null) cells, but less than 6% of autologous CD4(+)CD28(+) cells (P < 0.006). CD4(+)CD28(null) cells also had increased productions of proinflammatory cytokines, but less frequently expressed regulatory T-cell marker FoxP3 (2.1 +/- 1.3%), compared with autologous CD4(+)CD28(+) (9.5 +/- 1.4; P = 0.01). Cyclosporine A (100 ng/ml) inhibited proliferation of CD4(+)CD28(null) cells by 33 +/- 11% versus 68 +/- 12% inhibition of CD4(+)CD28(+) (P = 0.025). FEV(1) fell 6 months later (0.35 +/- 0.04 L) in recipients with CD4(+)CD28(+)/CD4(total) less than 90% (CD28% Low) compared with 0.08 +/- 0.08 L among CD4(+)CD28(+)/CD4(total) (CD28% High) greater than 90% (CD28% High) recipients (P = 0.013). Two-year freedom from death or retransplantation in CD28% Low recipients was 32 +/- 10% versus 78 +/- 6% among the CD28% High subjects (P < 0.0001). CONCLUSIONS: CD28 down-regulation on CD4 cells is associated with bronchiolitis obliterans syndrome and poor outcomes in lung transplantation recipients. CD4(+)CD28(null) cells have unusual, potentially pathogenic characteristics, and could be important in the progression of allograft dysfunction. These findings may illuminate a novel paradigm of transplantation immunopathogenesis, and suggest that CD28 measurements could identify recipients at risk for clinical deteriorations.

Decrements of body mass index are associated with poor outcomes of idiopathic pulmonary fibrosis patients.

BACKGROUND: The processes that result in progression of idiopathic pulmonary fibrosis (IPF) remain enigmatic. Moreover, the course of this disease can be highly variable and difficult to accurately predict. We hypothesized analyses of body mass index (BMI), a simple, routine clinical measure, may also have prognostic value in these patients, and might provide mechanistic insights. We investigated the associations of BMI changes with outcome, plasma adipokines, and adaptive immune activation among IPF patients. METHODS: Data were analyzed in an IPF discovery cohort (n = 131) from the University of Pittsburgh, and findings confirmed in patients from the University of Alabama at Birmingham (n = 148). Plasma adipokines were measured by ELISA and T-cell phenotypes determined by flow cytometry. RESULTS: Transplant-free one-year survivals in subjects with the greatest rates of BMI decrements, as percentages of initial BMI (>0.68%/month), were worse than among those with more stable BMI in both discovery (HR = 1.8, 95%CI = 1.1-3.2, p = 0.038) and replication cohorts (HR = 2.5, 95%CI = 1.2-5.2, p = 0.02), when adjusted for age, baseline BMI, and pulmonary function. BMI decrements >0.68%/month were also associated with greater mortality after later lung transplantations (HR = 4.6, 95%CI = 1.7-12.5, p = 0.003). Circulating leptin and adiponectin levels correlated with BMI, but neither adipokine was prognostic per se. BMI decrements were significantly associated with increased proportions of circulating end-differentiated (CD28null) CD4 T-cells (CD28%), a validated marker of repetitive T-cell activation and IPF prognoses. CONCLUSIONS: IPF patients with greatest BMI decrements had worse outcomes, and this effect persisted after lung transplantation. Weight loss in these patients is a harbinger of poor prognoses, and may reflect an underlying systemic process, such as adaptive immune activation.

Fortification of Preservation Solution With Nitroprusside Does Not Alter Lung Allograft Survival in Clinical Human Lung Transplantation.

Background: Nitric oxide improves gas exchange following primary lung allograft dysfunction. Nitroprusside, a potent nitric oxide donor, has reduced reperfusion injury and improved oxygenation in experimental lung transplantation. Methods: We sought to study the effect on lung allograft outcomes of fortifying the preservation solution with nitroprusside. We conducted a single-center clinical study of 46 consecutive lung recipients between 1998 and 2000: 24 patients received donor organs preserved in modified Euro-Collins solution with prostaglandin E1 (PGE1) (control group), and 22 patients received organs preserved in modified Euro-Collins with PGE1 and nitroprusside (NP group). The primary endpoint was overall survival. Results: Baseline characteristics were similar between the groups except for a significantly longer graft ischemic time in the NP group vs the control group (253.3 ± 52 vs 225.3 ± 41 minutes, respectively, P=0.04). No significant differences were found in partial pressure arterial oxygen to fraction inspired oxygen ratio at ≤48 hours, primary graft dysfunction, or bronchiolitis obliterans-free days. Overall survival at 1, 3, and 5 years was 89%, 73%, and 63% in the control group and 76%, 38%, and 23% in the NP group. Log-rank survival analysis showed that the NP group had a significantly increased risk of mortality (P=0.034) compared to the control group. Conclusion: The addition of nitroprusside to the lung transplant perfusate in this clinical trial did not improve survival; however, a large randomized trial would likely reduce confounding ischemia times and increase the power of the study.

Development and electronic validation of the revised Cystic Fibrosis Questionnaire (CFQ-R Teen/Adult): New tool for monitoring psychosocial health in CF.

BACKGROUND: The Cystic Fibrosis Questionnaire-Revised (CFQ-R+14) is a disease-specific, health-related quality of life instrument for cystic fibrosis (CF) patients ≥14years. We have developed a Spanish electronic version of the CFQ-R (e-CFQ-R+14 Spain). Our aim was to compare the paper and electronic versions and to validate the electronic version. METHODS: Fifty CF patients completed the study. All answered the paper and electronic versions on day 1 and repeated the e-CFQR version 15days later. RESULTS: Concordance between the electronic and paper copy versions was high, with correlations above 0.9 in all domains. Test-retest reliability of the e-CFQ-R results was strong, with coefficients ranging from 0.8 to 0.9. CONCLUSIONS: The e-CFQ-R version is reliable and valid and can replace the paper copy, thus simplifying the assessment of quality of life. It also provides immediate results with no errors in scoring. It is a useful new tool in CF care.

Durability of Sirolimus for Lymphangioleiomyomatosis.

Lymphangioleiomyomatosis (LAM), a rare, multisystem disorder primarily affecting women of reproductive age, is characterized by cystic-appearing lung lesions, progressive loss of lung function, chylous effusions and renal angiomyolipomas. Sirolimus, an mammalian target of rapamycin inhibitor, has been shown to stabilize lung function, reduce symptoms and resolve chylous effusions in the short term for patients with LAM. Herein, we report a premenopausal female with LAM who experienced complete and durable resolution of her chylothoraces with significant and sustained improvement in lung function on sirolimus.

CFTR targeting during activation of human neutrophils.

Cystic fibrosis transmembrane conductance regulator (CFTR), a cAMP-activated chloride channel, plays critical roles in phagocytic host defense. However, how activated neutrophils regulate CFTR channel distribution subcellularly is not well defined. To investigate, we tested multiple Abs against different CFTR domains, to examine CFTR expression in human peripheral blood neutrophils by flow cytometry. The data confirmed that resting neutrophils had pronounced CFTR expression. Activation of neutrophils with soluble or particulate agonists did not significantly increase CFTR expression level, but induced CFTR redistribution to cell surface. Such CFTR mobilization correlated with cell-surface recruitment of formyl-peptide receptor during secretory vesicle exocytosis. Intriguingly, neutrophils from patients with ΔF508-CF, despite expression of the mutant CFTR, showed little cell-surface mobilization upon stimulation. Although normal neutrophils effectively targeted CFTR to their phagosomes, ΔF508-CF neutrophils had impairment in that process, resulting in deficient hypochlorous acid production. Taken together, activated neutrophils regulate CFTR distribution by targeting this chloride channel to the subcellular sites of activation, and ΔF508-CF neutrophils fail to achieve such targeting, thus undermining their host defense function.

Long-term survival in lung transplant recipients after successful preoperative coronary revascularization.

OBJECTIVE: Coronary artery disease is considered a contraindication to lung transplantation. We studied effect of pre-lung transplantation nonobstructive coronary artery disease and revascularized coronary artery disease on long-term lung transplant survival. METHODS: Clinical courses of 172 lung transplant recipients from December 1990 to May 2003 were reviewed. Significant coronary artery disease, defined as left main stenosis of greater than 50% or other epicardial vessel stenosis of greater than 70%, was present in 7 patients; 6 received percutaneous coronary intervention and 1 received coronary artery bypass grafting before transplantation. RESULTS: Groups were similar with regard to sex, race, or length of intensive care days. The group with normal coronary arteries was significantly younger than the groups with coronary artery disease. The revascularized group had a significant increase in dysrhythmias (P < .003) and 1-, 3-, and 5-year survivals of 85%, 85%, and 69%, respectively. Those with insignificant coronary artery disease (14 patients) demonstrated a 1-, 3-, and 5-year survival of 64%, 40%, and 32%, respectively. The normal coronary group (151 patients) had a 1-, 3-, and 5-year survival of 75%, 58%, and 40%, respectively. The revascularized group had a significant survival advantage compared with that of the insignificant coronary artery disease group (P < .04, log-rank test). CONCLUSION: Long-term survival of lung transplant recipients with revascularized coronary arteries is similar to that of subjects with normal coronary arteries, despite an increased incidence of dysrhythmias. Lung transplant recipients with insignificant coronary artery disease had a worse survival than the revascularized group. More studies are needed to ascertain the cause and determine the optimal management for lung transplant recipients with insignificant coronary artery disease.

Pectus excavatum with inspiratory inferior vena cava compression: a new presentation of pulsus paradoxus.

A 29-year-old man with pectus excavatum presented with exercise intolerance, pulsus paradoxus, and paradoxically split S2. Chest computed tomography (CT) showed the heart shifted leftward and a pectus severity index of 7.18. Cardiopulmonary exercise study showed reduced VO2max, anaerobic threshold, and oxygen pulse. Echocardiography revealed a decline in mitral and tricuspid valve inflow, and stroke volume during inspiration. Cardiac extrinsic compression and anatomic cardiac abnormalities were not present. Dynamic magnetic resonance imaging (MRI) demonstrated inspiratory inferior vena cava (IVC) compression at the diaphragm. We discuss IVC compression by the diaphragm as a source of patient symptoms and as a mechanism for pulsus paradoxus associated with pectus excavatum.

Reliability of diagnostic criteria for bronchiolitis obliterans syndrome after lung transplantation: a survey.

BACKGROUND: Long-term outcomes after lung transplantation are limited due to chronic lung allograft dysfunction (CLAD). Bronchiolitis obliterans syndrome (BOS) is the most common form of obstructive CLAD and its definition derives from spirometric measurements. Given the importance of this diagnosis, both the accuracy and reliability of the definition of CLAD are crucial in understanding the pathophysiology of this disease to develop therapeutic options and influence outcome after lung transplantation. METHODS: A web-based survey was designed and distributed to members of the Pulmonary Council of the International Society for Heart and Lung Transplantation (ISHLT) to better understand the accuracy and reliability of pulmonary function criteria in diagnosing BOS. Spirometric data from five patient scenarios that were discordant among reviewers regarding BOS determination from the Assessment of Immunosuppressive Regimen in Suppressing Acute and Chronic Rejection (AIRSAC) trial were randomly selected and summarized in this survey. Survey questions included the respondent's general understanding of the BOS definition, the determination of BOS, and difficulties with the current BOS definition. RESULTS: Eighty-seven respondents from the Pulmonary Council of the ISHLT responded to this survey. There was an overall 70% interobserver agreement regarding the presence or absence of BOS. Among those who agreed upon the presence of BOS, there was a 41% interobserver agreement regarding its time of onset. Despite this variability, the majority of respondents were not only familiar and agreed with the BOS criteria, they also felt confident in applying these criteria. CONCLUSIONS: Our survey identified potential limitations with the current criteria for diagnosing BOS. With recognition of the various CLAD phenotypes, further refinements of these diagnostic criteria will allow for an improved ability to identify and characterize patients who develop or are at risk for BOS, prognosticate outcomes, and, most importantly, marshal in future strategies directed at treating and preventing chronic lung dysfunction after lung transplantation.

Muddying the water for a clear diagnosis.

Pulmonary sporotrichosis, such as other chronic fungal and mycobacterial infections, can be difficult to diagnose. We present a novel twist on the old technique of bronchoalveolar lavage that leads to improved diagnostic yield.