Rapidly progressive respiratory failure after helminth larvae ingestion.

BACKGROUND: Self-administration of helminths has gained attention among patients as a potential but unproven therapy for autoimmune disease. We present a case of rapidly progressive respiratory failure in a patient with systemic sclerosis (SSc) and pulmonary arterial hypertension (PAH) as a result of self-administration of parasitic organisms. CASE: A 45-year-old woman with a history of interstitial lung disease and PAH due to limited cutaneous SSc presented to pulmonary clinic with worsening dyspnea, cough, and new onset hypoxemia. Three months prior to presentation she started oral helminth therapy with Necator americanus as an alternative treatment for SSc. Laboratory evaluation revelaed eosinophilia and elevated IgE levels. IgG antibodies to Strongyloides were detected. High resolution computed tomography of the chest revealed progressive ILD and new diffuse ground glass opacities. Transthoracic echocardiogram and right heart catheterization illustrated worsening PAH and right heart failure. The patient was admitted to the hospital and emergently evaluated for lung transplantation but was not a candidate for transplantation due to comorbidities. Despite aggressive treatment for PAH and right heart failure, her respiratory status deteriorated, and the patient transitioned to comfort-focused care. CONCLUSION: Although ingestion of helminths poses a risk of infection, helminth therapy has been investigated as a potential treatment for autoimmune diseases. In this case, self-prescribed helminth ingestion precipitated fatal acute worsening of lung inflammation, hypoxemia, and right heart dysfunction, highlighting the risk of experimental helminth therapy in patients, especially those with underlying respiratory disease.

Utility of Bronchoalveolar Lavage and Transbronchial Biopsy in Patients with Interstitial Lung Disease.

PURPOSE: Bronchoalveolar lavage and transbronchial biopsy can be a useful tool in the evaluation of interstitial lung disease (ILD), but patient selection for this procedure remains poorly defined. Determining clinical characteristics that help with patient selection for bronchoscopy may improve confidence of ILD classification while limiting potential adverse outcomes associated with surgical lung biopsy. The purpose of this study is to identify factors that were associated with change in multidisciplinary ILD diagnosis (MDD) before and after incorporation of BAL and TBBx data. METHODS: We conducted a retrospective cohort study of ILD patients at a single center who underwent bronchoscopy in the diagnostic workup of ILD. We performed sequential MDD both pre- and post-bronchoscopy to calculate the frequency of change in diagnosis after incorporating information from BAL and TBBx and identify features associated with change in diagnosis. RESULTS: 245 patients were included in the study. Bronchoscopy led to a change in diagnosis in 58 patients (23.7%). The addition of TBBx to BAL increased diagnostic yield from 21.8 to 34.1% (p = 0.027). Identification of antigen, HRCT scan inconsistent with UIP, and absence of a pre-bronchoscopy diagnosis of CTD-ILD or IPAF were associated with a change in diagnosis after bronchoscopy. CONCLUSION: Our study suggests clinical features that may assist with patient selection for bronchoscopy. We suggest bronchoscopy in patients with identified antigen or an HRCT that is consistent with a non-IPF diagnosis. Appropriate patient selection for bronchoscopy may improve ILD diagnostic confidence and avoid potential complications from more invasive and higher risk procedures.

A case report of phenytoin-induced eosinophilic pneumonia.

Eosinophilic pneumonia comprises a rare and potentially serious group of lung diseases characterized by abnormal accumulation of eosinophils in the lungs. Many medications including the anticonvulsant phenytoin, have been implicated in the development of eosinophilic pneumonia. Attributing eosinophilic pneumonia to a medication or toxin can be difficult and may only be achieved by exclusion. The process can be particularly challenging in polypharmacy and when there has been long-term use. Notwithstanding, the presence of a potential offending drug/agent, exclusion of other causes of eosinophilic pneumonia, clinical improvement after cessation of the offending agent, or return of eosinophilic pneumonia after re-challenge are strong indicators for a drug-induced diagnosis. We report a case of phenytoin-induced eosinophilic pneumonia that resolved after medication withdrawal. Considering drug toxicity as a possible etiology of eosinophilic pneumonia is important to allow for the prompt removal of the causative agent, which can result in clinical cure.

Long-Term Treatment With Azathioprine and Mycophenolate Mofetil for Myositis-Related Interstitial Lung Disease.

BACKGROUND: The efficacy of azathioprine (AZA) and mycophenolate mofetil (MMF) for interstitial lung disease (ILD) has been described, but mainly in connective tissue disease-associated ILD. The objective of this study was to evaluate the effect of AZA and MMF on lung function and prednisone dose in myositis-related ILD (M-ILD). METHODS: In this retrospective study, patients with M-ILD seen at Johns Hopkins and treated with AZA or MMF and no other steroid-sparing agents were included. Linear mixed-effects models adjusted for sex, age, antisynthetase antibody, and smoking status were used to compare the change in FVC % predicted, diffusing capacity of the lungs for carbon monoxide (Dlco) % predicted, and prednisone dose. RESULTS: Sixty-six patients with M-ILD were treated with AZA and 44 with MMF. At treatment initiation, mean FVC % predicted and Dlco % predicted were significantly lower in the AZA group than in the MMF group. In both groups, FVC % predicted improved and the prednisone dose was reduced over 2 to 5 years; however, for Dlco % predicted, only the AZA group improved. The adjusted model showed no significant difference in posttreatment FVC % predicted or Dlco % predicted between groups (mean difference of 1.9 and -8.2, respectively), but a 6.6-mg lower dose of prednisone at 36 months in the AZA group. Adverse events were more frequent with AZA than MMF (33.3% vs 13.6%; P = .04). CONCLUSIONS: In M-ILD, AZA treatment was associated with improved FVC % predicted and Dlco % predicted, and lower prednisone dose. Patients treated with MMF had improved FVC % predicted and lower prednisone dose. After 36 months, patients treated with AZA received a lower prednisone dose than those treated with MMF.

Pirfenidone-induced hyponatraemia: insight in mechanism, risk factor and management.

Pirfenidone was approved in October 2014 in the USA for the treatment of idiopathic pulmonary fibrosis. Although not included in the adverse events published in the CAPACITY-1 and CAPACITY-2 or ASCEND trials, hyponatraemia was reported in supplementary data with rate of 3.4% in the active therapy arm versus 0.3% in the placebo arm. We performed a retrospective analysis of patients who were initiated on pirfenidone or nintedanib for the treatment of pulmonary fibrosis at our centre. Of the 52 patients who were started on pirfenidone, three (5.8%) developed severe hyponatraemia. Of the 29 patients who were started on nintedanib, none developed hyponatraemia. Laboratory data suggested syndrome of inappropriate antidiuretic hormone secretion (SIADH) induced by pirfenidone and the medication was discontinued. Hyponatraemia is a possible significant adverse effect of pirfenidone, able to induce SIADH in patients taking the medication.

A longitudinal cohort study of the anti-synthetase syndrome: increased severity of interstitial lung disease in black patients and patients with anti-PL7 and anti-PL12 autoantibodies.

Objective: The aim was to study the prevalence, rate of appearance and severity of clinical features in patients with different anti-synthetase syndrome (ASyS) autoantibodies. Methods: All Johns Hopkins Myositis Longitudinal Cohort subjects positive for any ASyS autoantibodies were included. Clinical information, including symptoms, signs, strength, creatine kinase concentrations and pulmonary function tests, were prospectively collected. The standardized mortality and cancer rates and the rate of appearance and intensity of the different organ manifestations were assessed using univariate and multivariate analysis and compared between ASyS autoantibodies. Results: One hundred and twenty-four (73.4%) patients were positive for anti-Jo1, 23 (13.6%) for anti-PL12, 16 for anti-PL7 (9.5%) and 3 (1.8%) for anti-EJ or anti-OJ, respectively. The mean length of follow-up was 4.1 years. Anti-PL12 was more frequent in black subjects. Anti-PL12 and anti-PL7 were associated with more prevalent and severe lung involvement, often without muscle involvement. Anti-Jo1 displayed more severe muscle involvement compared with anti-PL12 patients. Concurrent anti-Ro52 was more prevalent in anti-Jo1 patients and was associated with earlier development of mechanic's hands, DM-specific skin findings and arthritis. Independent of ASyS antibody status, black patients demonstrated more severe lung involvement than white patients. There was no significant increase in mortality or cancer risk in ASyS patients compared with the general US population. Conclusion: Different ASyS autoantibodies are associated with phenotypically distinct subgroups within the ASyS spectrum. Anti-PL7 and anti-PL12 are characterized by more severe lung involvement, whereas anti-Jo1 is associated with more severe muscle involvement. Black race is a major prognostic factor associated with lung disease severity.

Human Immunodeficiency Virus and Allergic Bronchopulmonary Aspergillosis: Case Report and Review of Literature.

Allergic bronchopulmonary aspergillosis (ABPA) results from a hypersensitivity response to airways colonization with Aspergillus fumigatus, and it occurs most often in individuals with asthma or cystic fibrosis. Allergic bronchopulmonary aspergillosis is an indolent, but potentially progressive, disease in patients. In patients infected with human immunodeficiency virus (HIV), ABPA is rare, and its description in the literature is limited to case reports. We describe the occurrence of ABPA in a 37-year-old woman with well controlled HIV infection. This represents the first documented case of ABPA in an HIV-infected patient whose only pulmonary comorbidity included the ramifications of prior acute respiratory distress syndrome due to Pneumocystis jirovecii pneumonia. We also review prior case reports of ABPA in HIV-infected patients and consider risk factors for its development.

A novel risk score that incorporates recipient and donor variables to predict 1-year mortality in the current era of lung transplantation.

BACKGROUND: In this study we sought to construct a novel scoring system to pre-operatively stratify a patient's risk of 1-year mortality after lung transplantation (LTx) based on recipient- and donor-specific characteristics. METHODS: The UNOS database was queried for adult (≥18 years) patients undergoing LTx between May 1, 2005 and December 31, 2012. The population was randomly divided in a 4:1 fashion into derivation and validation cohorts. A multivariable logistic regression model for 1-year mortality was constructed within the derivation cohort. Points were then assigned to independent predictors (p < 0.05) based on relative odds ratios. Risk groups were established based on score ranges. RESULTS: During the study period, 9,185 patients underwent LTx and the 1-year mortality was 18.0% (n = 1,654). There was a similar distribution of variables between the derivation (n = 7,336) and validation (n = 1,849) cohorts. Of the 14 covariates included in the final model, 9 were ultimately allotted point values (maximum score = 70). The model exhibited good predictive strength (c = 0.65) in the derivation cohort and demonstrated a strong correlation between the observed and expected rates of 1-year mortality in the validation cohort (r = 0.87). The low-risk (score 0 to 11), intermediate-risk (score 12 to 21) and high-risk (score ≥22) groups had a 10.8%, 17.1% and 32.0% risk of mortality (p < 0.001), respectively. CONCLUSIONS: This is the first scoring system that incorporates both recipient- and donor-related factors to predict 1-year mortality after LTx. Its use could assist providers in the identification of patients at highest risk for poor post-transplant outcomes.

Lung transplantation in telomerase mutation carriers with pulmonary fibrosis.

Lung transplantation is the only intervention that prolongs survival in idiopathic pulmonary fibrosis (IPF). Telomerase mutations are the most common identifiable genetic cause of IPF, and at times, the telomere defect manifests in extrapulmonary disease such as bone marrow failure. The relevance of this genetic diagnosis for lung transplant management has not been examined. We gathered an international series of telomerase mutation carriers who underwent lung transplant in the U.S.A., Australia and Sweden. The median age at transplant was 52 years. Seven recipients are alive with a median follow-up of 1.9 years (range 6 months to 9 years); one died at 10 months. The most common complications were haematological, with recipients requiring platelet transfusion support (88%) and adjustment of immunosuppressives (100%). Four recipients (50%) required dialysis for tubular injury and calcineurin inhibitor toxicity. These complications occurred at significantly higher rates relative to historic series (p<0.0001). Our observations support the feasibility of lung transplantation in telomerase mutation carriers; however, severe post-transplant complications reflecting the syndromic nature of their disease appear to occur at higher rates. While these findings need to be expanded to other cohorts, caution should be exercised when approaching the transplant evaluation and management of this subset of pulmonary fibrosis patients.

Circadian rhythm disruption in severe sepsis: the effect of ambient light on urinary 6-sulfatoxymelatonin secretion.

PURPOSE: Properly regulated circadian rhythm supports physical and immunologic function. This rhythm is disrupted in patients with critical illness. We assessed the association between ambient light and circadian melatonin release, measured by urinary 6-sulfatoxymelatonin (6-SMT), in medical intensive care unit (MICU) patients with severe sepsis. METHODS: After excluding patients for renal failure or hepatic failure, blindness, and intracranial disease, seven patients were studied. No environmental manipulation was performed. Urinary 6-SMT specimens were obtained every 4 h. Light was measured in 1-min epochs for two sequential 24-h periods and compared to 6-SMT levels. RESULTS: No significant differences among urinary 6-SMT levels were found across 4-h time periods or between the 2 days (range 1,190.26 ± 1,040.81­4,738.57 ± 5,543.08 ng, 4-h period p = 0.09, 24-h day p = 0.50). Light levels were low and differed among 4-h periods, but not 24-h averages (minimum 2.32 ± 3.65 lux/min 00:01­04:00, maximum 70.11 ± 79.12 lux/min from 12:01­16:00, 4 h period p = <0.001, 24 h period p = 0.53). There was no relationship between light levels and 6-SMT excretion. CONCLUSIONS: Circadian rhythm was disrupted in patients with severe sepsis, as reflected by disordered diurnal variation of urinary 6-SMT excretion. Light levels were low, exhibited limited diurnal variation, and did not entrain circadian rhythms in these patients.