ABSTRACT
BACKGROUND: Airway stenting may be needed to manage anastomotic complications in lung transplant recipients. Conventional stenting strategies may be inadequate due to anatomic variations between the recipient and donor or involvement of both the anastomosis and lobar bronchi. METHODS: We investigated the efficacy of 3D-designed patient-specific silicone Y-stents in managing this scenario. 9 patients with complex airway stenosis underwent custom stent insertion after either failing traditional management strategies or having anatomy not suitable for conventional stents. CT images were uploaded to stent design software to make a virtual stent model. 3D printing technology was then used to make a mold for the final silicone stent which was implanted via rigid bronchoscopy. Forced expiratory volume in 1 s (FEV1) was measured pre- and post-stent placement. RESULTS: 78 % of patients experienced an increase in their FEV1 after stent insertion, (p = 0.001, 0.02 at 30 and 90 days respectively). Unplanned bronchoscopies primarily occurred due to mucous plugging. 2 patients had sufficient airway remodeling allowing for stent removal. CONCLUSIONS: Personalized 3D-designed Y-stents demonstrate promising results for managing complicated airway stenosis, offering improved lung function and potential long-term benefits for lung transplant recipients.
Subject(s)
Bronchoscopy , Lung Transplantation , Silicones , Stents , Humans , Lung Transplantation/adverse effects , Male , Female , Constriction, Pathologic/surgery , Constriction, Pathologic/etiology , Middle Aged , Bronchoscopy/methods , Adult , Printing, Three-Dimensional , Anastomosis, Surgical/adverse effects , Forced Expiratory Volume , Postoperative Complications/etiology , Tomography, X-Ray Computed , Aged , Transplant RecipientsSubject(s)
Acetates , Antiviral Agents , Cytomegalovirus Infections , Lung Transplantation , Quinazolines , Humans , Cytomegalovirus Infections/prevention & control , Lung Transplantation/adverse effects , Antiviral Agents/therapeutic use , Antiviral Agents/adverse effects , Acetates/therapeutic use , Acetates/adverse effects , Acetates/administration & dosage , Quinazolines/therapeutic use , Quinazolines/adverse effects , Cytomegalovirus/drug effects , Triazoles/therapeutic use , Triazoles/adverse effects , Triazoles/administration & dosage , Transplant RecipientsABSTRACT
Clinical prediction of nontuberculous mycobacteria lung disease (NTM-LD) progression remains challenging. We aimed to evaluate antigen-specific immunoprofiling utilizing flow cytometry (FC) of activation-induced markers (AIM) and IFN-γ enzyme-linked immune absorbent spot assay (ELISpot) accurately identifies patients with NTM-LD, and differentiate those with progressive from nonprogressive NTM-LD. A Prospective, single-center, and laboratory technician-blinded pilot study was conducted to evaluate the FC and ELISpot based immunoprofiling in patients with NTM-LD (n = 18) and controls (n = 22). Among 18 NTM-LD patients, 10 NTM-LD patients were classified into nonprogressive, and 8 as progressive NTM-LD based on clinical and radiological features. Peripheral blood mononuclear cells were collected from patients with NTM-LD and control subjects with negative QuantiFERON results. After stimulation with purified protein derivative (PPD), mycobacteria-specific peptide pools (MTB300, RD1-peptides), and control antigens, we performed IFN-γ ELISpot and FC AIM assays to access their diagnostic accuracies by receiver operating curve (ROC) analysis across study groups. Patients with NTM-LD had significantly higher percentage of CD4+/CD8+ T-cells co-expressing CD25+CD134+ in response to PPD stimulation, differentiating between NTM-LD and controls. Among patients with NTM-LD, there was a significant difference in CD25+CD134+ co-expression in MTB300-stimulated CD8+ T-cells (p <0.05; AUC-ROC = 0.831; Sensitivity = 75% [95% CI: 34.9-96.8]; Specificity = 90% [95% CI: 55.5-99.7]) between progressors and nonprogressors. Significant differences in the ratios of antigen-specific IFN-γ ELISpot responses were also seen for RD1-nil/PPD-nil and RD1-nil/anti-CD3-nil between patients with nonprogressive vs. progressive NTM-LD. Our results suggest that multiparameter immunoprofiling can accurately identify patients with NTM-LD and may identify patients at risk of disease progression. A larger longitudinal study is needed to further evaluate this novel immunoprofiling approach.
Subject(s)
Mycobacterium Infections, Nontuberculous , Pneumonia , Humans , Pilot Projects , Prospective Studies , Leukocytes, Mononuclear , Mycobacterium Infections, Nontuberculous/microbiology , Nontuberculous MycobacteriaABSTRACT
PURPOSE OF THE REVIEW: This study aimed to summarize evidence and provide consensus-based guidelines for management of transplantation in patients with telomere biology disorders (TBD). Specifically, this review focuses on clinical management of lung, liver, and bone marrow transplantation in TBD patients. RECENT FINDINGS: TBD patients have specific unique biological vulnerabilities such as T cell immunodeficiency, susceptibility to infections, hypersensitivity to chemotherapy and radiation, and cytopenias. Furthermore, multiple organ involvement at diagnosis makes clinical management especially challenging due to higher degree of organ damage, and stress-induced telomeric crisis. Sequential and combined organ transplants, development of novel radiation and alkylator-free conditioning regimen, and use of novel drugs for graft-versus-host disease prophylaxis are some of the recent updates in the field. Multidisciplinary management is essential to optimize transplant outcomes in patients with TBD. In this review, we provide consensus-based transplant management guidelines for clinical management of transplant in TBD.
ABSTRACT
BACKGROUND: Diffusing capacity (DLCO) measurements are affected by hemoglobin. Two adjustment equations are used: Cotes (recommended by ATS/ERS) and Dinakara (used in the hematopoietic stem cell transplantation comorbidity index [HCT-CI]). It is unknown how these methods compare, and which is better from a prognostication standpoint. STUDY DESIGN: This is a retrospective cohort of 1273 adult patients who underwent allogeneic HCT, completed a pre-transplant DLCO and had a concurrent hemoglobin measurement. Non-relapse mortality was measured using competing risk analysis. RESULTS: Patients had normal spirometry (FEV1 99.7% [IQR: 89.4-109.8%; FVC 100.1% [IQR: 91.0-109.6%] predicted), left ventricular ejection fraction (57.2[6.7]%) and right ventricular systolic pressure (30.1[7.0] mmHg). Cotes-DLCO was 85.6% (IQR: 76.5-95.7%) and Dinakara-DLCO was 103.6% (IQR: 90.7-117.2%) predicted. For anemic patients (Hb<10g/dL), Cotes-DLCO was 84.2% (IQR: 73.9-94.1%) while Dinakara-DLCO 111.0% (97.3-124.7%) predicted. Cotes-DLCO increased HCT-CI score for 323 (25.4%) and decreased for 4 (0.3%) patients. Cotes-DLCO was superior for predicting non-relapse mortality: for both mild (66-80% predicted, HR 1.55 [95%CI: 1.26-1.92, p < 0.001]) and moderate (<65% predicted, HR 2.11 [95%CI: 1.55-2.87, p<0.001]) impairment. In contrast, for Dinakara-DLCO, only mild impairment (HR 1.69 [95%CI 1.26-2.27, p < 0.001]) was associated with lower survival while moderate impairment was not (HR 1.44 [95%CI: 0.64-3.21, p = 0.4]). In multivariable analyses, after adjusting for demographics, hematologic variables, cardiac function and FEV1, Cotes-DLCO was predictive of overall survival at 1-year (OR 0.98 [95%CI: 0.97-1.00], p = 0.01), but Dinakara-DLCO was not (OR 1.00 [95%CI: 0.98-1.00], p = 0.20). CONCLUSION: The ERS/ATS recommended Cotes method likely underestimates DLCO in patients with anemia, whereas the Dinakara (used in the HCT-CI score) overestimates DLCO. The Cotes method is superior to the Dinakara method score in predicting overall survival and relapse-free survival in patients undergoing allogeneic HCT.
Subject(s)
Anemia , Hematopoietic Stem Cell Transplantation , Pulmonary Diffusing Capacity , Transplantation, Homologous , Humans , Male , Anemia/epidemiology , Anemia/therapy , Female , Middle Aged , Hematopoietic Stem Cell Transplantation/adverse effects , Retrospective Studies , Adult , Pulmonary Diffusing Capacity/physiology , Transplantation, Homologous/adverse effects , Hemoglobins/analysis , Aged , PrognosisABSTRACT
BACKGROUND: Invasive fungal infections are associated with high morbidity in solid organ transplant recipients. Risk factor modification may help with preventative efforts. The objective of this study was to identify risk factors for the development of fungal infections within the first year following solid organ transplant. METHODS: We searched for eligible articles through February 3, 2023. Studies published after January 1, 2001, that pertained to risk factors for development of invasive fungal infections in solid organ transplant were reviewed for inclusion. Of 3087 articles screened, 58 were included. Meta-analysis was conducted using a random-effects model to evaluate individual risk factors for the primary outcome of any invasive fungal infections and invasive candidiasis or invasive aspergillosis (when possible) within 1 y posttransplant. RESULTS: We found 3 variables with a high certainty of evidence and strong associations (relative effect estimate ≥ 2) to any early invasive fungal infections across all solid organ transplant groups: reoperation (odds ratio [OR], 2.92; confidence interval [CI], 1.79-4.75), posttransplant renal replacement therapy (OR, 2.91; CI, 1.87-4.51), and cytomegalovirus disease (OR, 2.97; CI, 1.78-4.94). Both posttransplant renal replacement therapy (OR, 3.36; CI, 1.78-6.34) and posttransplant cytomegalovirus disease (OR, 2.81; CI, 1.47-5.36) increased the odds of early posttransplant invasive aspergillosis. No individual variables could be pooled across groups for invasive candidiasis. CONCLUSIONS: Several common risk factors exist for the development of any invasive fungal infections in solid organ transplant recipients. Additional risk factors for invasive candidiasis and aspergillosis may be unique to the pathogen, transplanted organ, or both.
Subject(s)
Aspergillosis , Candidiasis, Invasive , Candidiasis , Cytomegalovirus Infections , Invasive Fungal Infections , Organ Transplantation , Humans , Risk Factors , Organ Transplantation/adverse effects , Cytomegalovirus Infections/complications , Invasive Fungal Infections/diagnosis , Invasive Fungal Infections/epidemiology , Invasive Fungal Infections/etiology , Candidiasis, Invasive/complications , Transplant RecipientsABSTRACT
CONTEXT.: Respiratory infections complicate lung transplantation and increase the risk of allograft dysfunction. Allograft lungs may have different susceptibilities to infection than native lungs, potentially leading to different disease severity in lungs of single lung transplant recipients (SLTRs). OBJECTIVE.: To study whether infections affect allograft and native lungs differently in SLTRs but similarly in double LTRs (DLTRs). DESIGN.: Using an institutional database of LTRs, medical records were searched, chest computed tomography studies were systematically reviewed, and histopathologic features were recorded per lung lobe and graded semiquantitatively. A multilobar-histopathology score (MLHS) including histopathologic data from each lung and a bilateral ratio (MLHSratio) comparing histopathologies between both lungs were calculated in SLTRs and compared to DLTRs. RESULTS.: Six SLTRs died of infection involving the lungs. All allografts showed multifocal histopathologic evidence of infection, but at least 1 lobe of the native lung was uninvolved. In all 5 DLTRs except 1, histopathologic evidence of infection was seen in all lung lobes. On computed tomography, multifocal ground-glass and/or nodular opacities were found in a bilateral distribution in all DLTRs but in only 2 of 6 SLTRs. In SLTRs, the MLHSAllograft was higher than MLHSNative (P = .02). The MLHSratio values of SLTR and DLTR were significantly different (P < .001). CONCLUSIONS.: Allograft and native lungs appear to harbor different susceptibilities to infections. The results are important for the management of LTRs.
ABSTRACT
Extracorporeal membrane oxygenation is used as a bridge to transplant (ECMO-BTT) in selected patients. The objective of this study was to determine whether 1-year post-transplant and post-ECMO survival are impacted by traditional compared to expanded selection criteria. We performed a retrospective study of patients >17 years who received ECMO as bridge to transplant (BTT) or bridge to transplant decision for lung or combined heart and lung transplantation at the Mayo Clinic Florida and Rochester. Institutional protocol excludes patients >55 years, maintained on steroids, unable to participate in physical therapy, with body mass index >30 or <18.5 kg/m2, non-pulmonary end-organ dysfunction, or unmanageable infections from ECMO-BTT. For this study, adherence to this protocol was considered traditional whereas exceptions to the protocol were considered expanded selection criteria. A total of 45 patients received ECMO as bridge therapy. Out of those 29 patients (64%) received ECMO as bridge to transplant and 16 patients (36%) as bridge to transplant decision. The traditional criteria cohort consisted of 15 (33%) patients and expanded criteria cohort consisted of 30 (67%) patients. In the traditional cohort, 9 (60%) of 15 patients were successfully transplanted compared to 16 (53%) of 30 patients in the expanded criteria cohort. No difference in being delisted or dying on the waitlist (OR: 0.58, CI: 0.13-2.58), surviving to 1-year post-transplant (OR: 0.53, CI: 0.03-9.71) or 1-year post-ECMO (OR: 0.77, CI: 0.0.23-2.56) was observed between the traditional criteria and expanded criteria cohorts. At our institution, we did not see differences in odds of 1-year post-transplant and post-ECMO survival between those who met traditional criteria compared to those who did not. Multicenter, prospective studies are needed to evaluate the impact of ECMO-BTT selection criteria.
ABSTRACT
BACKGROUND/OBJECTIVE: A subset of patients with idiopathic inflammatory myopathy (IIM) develops highly fatal, rapidly progressive interstitial lung disease (RP-ILD). Treatment strategies consist of glucocorticoid and adjunctive immunosuppressive therapies. Plasma exchange (PE) is an alternative therapy, but its benefit is unclear. In this study, we aimed to determine whether PE benefited outcomes for patients with RP-ILD. METHODS: In this medical records review study, we compared baseline characteristics and clinical outcomes for 2 groups of patients with IIM-related RP-ILD: those who received and did not receive PE. RESULTS: Our cohort consisted of 15 patients, 9 of whom received PE. Baseline demographic characteristics and severity of lung, skin, and musculoskeletal disease between the 2 groups of patients were not significantly different. Five patients required mechanical ventilation (2, PE; 3, no PE). Plasma exchange was generally a third-line adjunctive treatment option. The PE group had a longer median (interquartile range) hospitalization (27.0 [23.0-36.0] days) than the non-PE group (12.0 [8.0-14.0] days) ( p = 0.02). There was a potential benefit in 30-day mortality improvement in those receiving PE (0% vs 33%, p = 0.14), with a statistically significant improvement in 2 important composite end points including 30-day mortality or need for lung transplant (0% vs 50%, p = 0.04) and 1-year mortality or need for lung transplant or hospital readmission for RP-ILD in those receiving PE (22% vs 83%, p = 0.04). CONCLUSIONS: Plasma exchange may be an underutilized, safe salvage therapy for patients with IIM-related RP-ILD when other immunosuppressive therapies fail.
Subject(s)
Lung Diseases, Interstitial , Myositis , Humans , Plasma Exchange , Lung Diseases, Interstitial/therapy , Lung Diseases, Interstitial/complications , Myositis/complications , Myositis/therapy , Lung , Plasmapheresis , Autoantibodies , Retrospective StudiesABSTRACT
Incidence and prevalence of MAC infections are increasing globally, and reinfection is common. Thus, MAC infections present a significant public health challenge. We quantify the impact of MAC biofilms and repeated exposure on infection progression using a computational model of MAC infection in lung airways. MAC biofilms aid epithelial cell invasion, cause premature macrophage apoptosis, and limit antibiotic efficacy. In this computational work we develop an agent-based model that incorporates the interactions between bacteria, biofilm, and immune cells. In this computational model, we perform virtual knockouts to quantify the effects of the biofilm sources (deposited with bacteria vs. formed in the airway), and their impacts on macrophages (inducing apoptosis and slowing phagocytosis). We also quantify the effects of repeated bacterial exposures to assess their impact on infection progression. Our simulations show that chemoattractants released by biofilm-induced apoptosis bias macrophage chemotaxis towards pockets of infected and apoptosed macrophages. This bias results in fewer macrophages finding extracellular bacteria, allowing the extracellular planktonic bacteria to replicate freely. These spatial macrophage trends are further exacerbated with repeated deposition of bacteria. Our model indicates that interventions to abrogate macrophages' apoptotic responses to bacterial biofilms and/or reduce frequency of patient exposure to bacteria will lower bacterial load, and likely overall risk of infection.
Subject(s)
Mycobacterium avium , Mycobacterium tuberculosis , Humans , Bacterial Load , Macrophages/microbiology , Biofilms , Lung , Mycobacterium avium ComplexABSTRACT
BACKGROUND: Patients with structural lung disease and immunocompromised status are at increased risk of pulmonary non-tuberculous mycobacteria (NTM) infection. However, literature on NTM in lung transplant recipients (LTR) is limited. We sought to systematically review the literature and perform a meta-analysis to examine associations with NTM disease and isolation in LTRs and their influence on mortality and chronic lung allograft dysfunction (CLAD). METHODS: A literature search of MEDLINE and Embase was performed on February 23, 2022. NTM disease was defined according to international guidelines. Isolation was defined as any growth of NTM in culture. Odds ratios (OR) were pooled for risk factors of NTM disease or isolation, and hazard ratios (HR) were pooled for mortality or CLAD. RESULTS: Eleven studies totaling 3,371 patients were eligible for inclusion, 10 of which underwent meta-analysis. Cystic fibrosis (OR 1.84, 95% confidence interval [CI] 1.03-3.30; I2 = 0%) and pre-transplant NTM isolation (OR 2.40, 95% CI 1.20-4.83; I2 = 0%) were associated with NTM disease. Only male sex was associated with NTM isolation (OR 1.45, 95% CI 1.01-2.10; I2 = 0%). NTM disease was associated with increased mortality (HR 2.69, 95% CI 1.70-4.26; I2 = 0%) and CLAD (HR 2.11, 95% CI 1.03-4.35; I2 = 44%). NTM isolation was not associated with mortality in pooled analysis or CLAD in 1 included study. CONCLUSIONS: NTM disease, but not isolation, is associated with worse outcomes. Several factors were associated with development of NTM disease, including cystic fibrosis and pretransplant NTM isolation. Strategies to optimize prevention and treatment of NTM disease in lung transplant recipients are needed.
Subject(s)
Cystic Fibrosis , Lung Transplantation , Mycobacterium Infections, Nontuberculous , Humans , Male , Nontuberculous Mycobacteria , Mycobacterium Infections, Nontuberculous/epidemiology , Mycobacterium Infections, Nontuberculous/complications , Mycobacterium Infections, Nontuberculous/microbiology , Cystic Fibrosis/complications , Cystic Fibrosis/surgery , Transplant Recipients , Lung Transplantation/adverse effects , Retrospective Studies , Lung/microbiology , Risk FactorsABSTRACT
Objective: Innovative technology such as normothermic regional perfusion and the Organ Care System has expanded donation after circulatory death heart transplantation. We wanted to investigate the impact of donation after circulatory death heart procurement in concurrent lung donation and implantation at a national level. Methods: We reviewed the United Network for Organ Sharing database for heart donation between December 2019 and March 2022. Donation after circulatory death donors were separated from donation after brain death donors and further categorized based on concomitant organ procurement of lung and heart, or heart only. Results: A total of 8802 heart procurements consisted of 332 donation after circulatory death donors and 8470 donation after brain death donors. Concomitant lung procurement was lower among donation after circulatory death donors (19.3%) than in donation after brain death donors (38.0%, P < .001). The transplant rate of lungs in the setting of concomitant procurement is 13.6% in donation after circulatory death, whereas it is 38% in donation after brain death (P < .001). Of the 121 lungs from 64 donation after circulatory death donors, 22 lungs were retrieved but discarded (32.2%). Normothermic regional perfusion was performed in 37.3% of donation after circulatory death donors, and there was no difference in lung use between normothermic regional perfusion versus direct procurement and perfusion (20.2% and 18.8%). There was also no difference in 1-year survival between normothermic regional perfusion and direct procurement and perfusion. Conclusions: Although national use of donation after circulatory death hearts has increased, donation after circulatory death lungs has remained at a steady state. The implantation of lungs after concurrent procurement with the heart remains low, whereas transplantation of donation after circulatory death hearts is greater than 90%. The use of normothermic regional perfusion lungs has been controversial, and we report comparable 1-year outcomes to standard donation after circulatory death lungs. Further studies are warranted to investigate the underlying mechanisms of normothermic regional perfusion on lung function.
ABSTRACT
BACKGROUND: The incidence and impact of de novo fungal airway colonization and infection in lung transplant recipients (LTRs) with known chronic lung allograft dysfunction (CLAD) has not been established. We aimed to determine the 1-year cumulative incidence and risk factors of de novo fungal colonization or infection in LTRs with CLAD and assess the impact of colonization or infection on post-CLAD survival. METHODS: Prospectively collected Toronto Lung Transplant Program database and chart review were used for double-LTRs who were diagnosed with CLAD from January 1, 2016 to January 1, 2020 and who were free of airway fungi within 1 year prior to CLAD onset. International Society for Heart and Lung Transplantation definitions were used to define clinical syndromes. Cox-Proportional Hazards Models were used for risk-factor analysis. Survival analysis could not be completed secondary to low number of fungal events; therefore, descriptive statistics were employed for survival outcomes. RESULTS: We found 186 LTRs diagnosed with CLAD meeting our inclusion criteria. The 1-year cumulative incidence for any fungal event was 11.8% (7.0% for infection and 4.8% for colonization). Aspergillus fumigatus was a causative pathogen in eight of 13 (61.5%) patients with infection and six of nine (66.7%) patients with colonization. No patients with fungal colonization post-CLAD developed fungal infection. Peri-CLAD diagnosis (3 months prior or 1 month after) methylprednisolone bolus (hazards ratio: 8.84, p = .001) increased the risk of fungal events. Most patients diagnosed with fungal infections (53.8%) died within 1-year of CLAD onset. CONCLUSION: De novo IFIs and fungal colonization following CLAD onset were not common. Fungal colonization did not lead to fungal infection. Methylprednisolone bolus was a significant risk factors for post-CLAD fungal events.
Subject(s)
Lung Transplantation , Mycoses , Humans , Transplant Recipients , Retrospective Studies , Lung , Lung Transplantation/adverse effects , Mycoses/etiology , Allografts , Methylprednisolone/therapeutic useABSTRACT
BACKGROUND: Lung transplant recipients are at increased risk of candidemia, especially in the early posttransplant period. However, the specific predisposing factors have not been established. The natural history of candidemia after lung transplantation, in the absence of universal antifungal prophylaxis, is not known. METHODS: We retrospectively examined the epidemiology of candidemia at any time posttransplant in patients who underwent lung transplantation at our center between 2016 and 2019. We undertook a case-control study and used logistic regression to evaluate the risk factors for candidemia during the first 30 days posttransplantation. RESULTS: During the study period 712 lung transplants were performed on 705 patients. Twenty-five lung transplant recipients (LTRs) (3.5%) experienced 31 episodes of candidemia. The median time to candidemia was 19.5 days (IQR 10.5-70.5), with 61.2% (n = 19) episodes of candidemia occurring within the first 30 days posttransplantation. Pretransplant hospitalization, posttransplant ECMO, and posttransplant renal replacement therapy were associated with an increased risk of candidemia in the first 30 days posttransplant. Of those with candidemia in the first 30 days, 31.2% died within 30 days of the index positive blood culture. Candidemia was associated with decreased survival within 30 days posttransplant. CONCLUSION: This study highlights the greatest risk period of lung transplant recipients for development of candidemia and identifies several factors associated with increased risk of candidemia. These findings will help guide future studies on antifungal prophylaxis.
Subject(s)
Antifungal Agents , Candidemia , Antifungal Agents/therapeutic use , Candidemia/drug therapy , Candidemia/epidemiology , Candidemia/prevention & control , Case-Control Studies , Humans , Lung , Retrospective Studies , Risk Factors , Transplant RecipientsABSTRACT
Mycobacterium avium complex (MAC), is known for colonizing and infecting humans following inhalation of the bacteria. MAC pulmonary disease is notoriously difficult to treat and prone to recurrence. Both the incidence and prevalence MAC pulmonary disease have been increasing globally. MAC is well known to form biofilms in the environment. In vitro, these biofilms have been shown to aid MAC in epithelial cell invasion, protect MAC from phagocytosis, and cause premature apoptosis in macrophages. In vivo, the system of interactions between MAC, biofilms and host macrophages is complex, difficult to replicate in vitro and in animal models, has not been fully characterized. Here we present a three-dimensional agent-based model of a lung airway to help understand how these interactions evolve in the first 14 days post-bacterial inhalation. We parameterized the model using published data and performed uncertainty analysis to characterize outcomes and parameters' effects on those outcomes. Model results show diverse outcomes, including wide ranges of macrophage recruitment levels, and bacterial loads and phenotype distribution. Though most bacteria are phagocytosed by macrophages and remain intracellular, there are also many simulations in which extracellular bacteria continue to drive the colonization and infection. Initial parameters dictating host immune levels, bacterial loads introduced to the airway, and biofilm conditions have significant and lasting impacts on the course of these results. Additionally, though macrophage recruitment is key for suppressing bacterial loads, there is evidence of significant excess recruitment that fail to impact bacterial numbers. These results highlight a need and identify a path for further exploration into the inhalation events in MAC infection. Early infection dynamics could have lasting impacts on the development of nodular bronchiectatic or fibrocavitary disease as well as inform possible preventative and treatment intervention targeting biofilm-macrophage interactions.
Subject(s)
Mycobacterium avium Complex , Mycobacterium avium , Animals , Biofilms , Immunity, Innate , Mycobacterium avium Complex/genetics , PhenotypeABSTRACT
Lung transplantation in patients with systemic sclerosis (SSc) can be complicated by extrapulmonary manifestations of the disease, leading to concerns regarding posttransplant complications and outcomes. METHODS: We conducted a web-based survey of adult lung transplant programs in the United States regarding their practices in patients with SSc. RESULTS: Sixty percent (37/62) of the eligible centers responded to the survey, majority of the respondents were medical directors (81%). Most centers would consider transplanting patients with mild or moderate esophageal disease (92% or 75%, respectively) or gastroparesis (59%). A minority would consider patients with severe esophageal dysmotility (37%), digital ulcers (21%), or low body mass index (19%). Most centers conducted extensive pretransplant gastrointestinal evaluation and use a conservative feeding approach with prolonged nothing by mouth (83%) and postpyloric feeding (89%). Antireflux surgery is commonly considered (40%) with partial fundoplication being the procedure of choice (67%). Most respondents expected similar outcomes of acute or chronic rejection (81% and 51%, respectively), respiratory infections (76%), and 1-year survival (70%). CONCLUSIONS: Most US lung transplant centers do not universally exclude SSc from lung transplant listing, but most support extensive pretransplant gastrointestinal testing and a conservative approach to feeding in the early posttransplant period.
ABSTRACT
Pulmonary amyloidosis, whether isolated or seen as part of systemic amyloidosis, has a variety of radiographic manifestations. Known parenchymal lung findings include reticulonodular opacities, diffuse interstitial infiltrates, or cystic lesions. Here, we present a case of systemic amyloid light-chain (AL) amyloidosis presenting with severe exertional dyspnea and emphysematous lung lesions on chest CT, a finding described only once before. Although factors that influence the pattern of pulmonary amyloid deposition remain unclear, CT image findings typically reflect the histopathologic patterns of deposition. In this case, we hypothesize that the emphysematous changes in the lower lung zones are likely a manifestation of severe alveolar-septal involvement. This case suggests that radiographic findings of pulmonary amyloidosis are not limited to the more common findings of reticular opacities or interstitial infiltrates. Emphysematous changes are possible, and clinicians should maintain a broad differential when seen in the setting of dyspnea.
Subject(s)
Immunoglobulin Light-chain Amyloidosis/complications , Lung Diseases/complications , Pulmonary Emphysema/etiology , Aged , Biomarkers/blood , Biopsy , Female , Humans , Immunoglobulin G/blood , Immunoglobulin Light-chain Amyloidosis/diagnostic imaging , Lung Diseases/diagnostic imaging , Pulmonary Emphysema/diagnostic imaging , Tomography, X-Ray ComputedABSTRACT
Non-tuberculous mycobacteria (NTM) is a collective name given to a group of more than 190 species of Mycobacterium. The clinical presentation for most NTM infections is non-specific, often resulting in delayed diagnosis. Further complicating matters is that NTM organisms can be difficult to isolate. Medications used to treat NTM infection can be difficult for patients to tolerate, and prolonged courses of anti-mycobacterial therapy are often required for adequate suppression or eradication. Herein, we review different NTM syndromes, appropriate diagnostic tests, and treatment regimens.