Predictors and outcomes of respiratory failure among lung transplant patients with COVID-19.

BACKGROUND: There is limited data on the predictors and outcomes of new or worsening respiratory failure among lung transplant (LT) patients with Coronavirus disease 2019 (COVID-19). METHODS: We included all the LT patients diagnosed with COVID-19 during a 1-year period (March 2020 to February 2021; n = 54; median age: 60, 20-73 years; M:F 37:17). Development of new or worsening respiratory failure (ARF) was the primary outcome variable. RESULTS: The overall incidence of ARF was 48.1% (n = 26). More than 20% of patients (n = 11) needed intubation and mechanical ventilation. Body mass index > 25 Kg/m2 (adjusted OR: 5.7, .99-32.93; P = .05) and peak D-dimer levels > .95 mcg/ml (adjusted OR: 24.99, 1.77-353.8; P = .017) were independently associated with ARF while anticoagulation use prior to COVID-19 was protective (adjusted OR: .024, .001-.55; P = .02). Majority patients survived the acute illness (85.2%). Pre-infection chronic lung allograft dysfunction (CLAD) was an independent predictor of mortality (adjusted HR: 5.03, 1.14-22.25; P = .033). CONCLUSIONS: COVID-19 is associated with significant morbidity and mortality among LT patients. Patients on chronic anticoagulation seem to enjoy favorable outcomes, while higher BMI and peak D-dimer levels are associated with development of ARF. Pre-infection CLAD is associated with an increased risk of death from COVID-19.

Diaphragmatic plication among lung transplant patients: A single-center experience.

BACKGROUND: There is lack of data reporting outcomes among patients needing diaphragmatic plication (DP) during or after lung transplantation (LT). We sought to assess the association of DP with post-transplant spirometry among other outcomes. METHODS: We included all patients who underwent LT between 2012 and 2016 (n = 324, mean age 56.3±13.4 years; M:F 198:126). We compared early and late outcomes based on the need for DP. RESULTS: The frequency of diaphragmatic dysfunction (DD) on pre-transplant fluoroscopy was 52.2%. A total of 38 DP procedures were performed among 37 patients (11.4% of LT patients). DP was done for anatomic (sizing or spacing issues) or functional indications (symptomatic DD). While patients with DP had significantly lower spirometry throughout the 3-year follow-up period, their slope of decline, functional assessments at the first annual visit, the risk of CLAD, and mortality were similar to patients without DP. A sub-group analysis limited to patients with restrictive lung diseases as the transplant indication had similar findings. CONCLUSIONS: Pre-transplant DD is common among LT candidates although it did not predict the need for DP. DP may be performed for functional or anatomic indications especially for addressing the donor-recipient size mismatch. Despite the lack of favorable effect on post-transplant spirometry, patients undergoing DP have acceptable and comparable early and late outcomes.

Characteristics and outcomes among vaccinated lung transplant patients with breakthrough COVID-19.

BACKGROUND: Despite multiple studies evaluating the immunological responsiveness to vaccines, the clinical effectiveness of the two-dose mRNA vaccine schedule among lung transplant (LT) patients has not been evaluated. METHODS: We included LT patients who tested positive for SARS-CoV-2 on a nasopharyngeal swab between March 1, 2020, and August 25, 2021 (n = 70). The study group was divided based on their vaccination status. RESULTS: During the study period, 14 fully vaccinated LT patients with one of the mRNA vaccines tested positive for COVID-19 (median age 54, range 30-62 years, M:F 9:5). The vaccinated cohort was younger with bilateral LT, have suppurative conditions as the transplant indication, and present with milder symptoms. However, pulmonary parenchymal involvement was seen among all 12 patients where computed tomography (CT) of chest was available. The laboratory profile indicated a more subdued inflammatory response among the vaccinated group. A lower proportion of vaccinated patients developed respiratory failure, needed ICU admission or ventilator support, although none of the differences achieved statistical significance. None of the vaccinated patients succumbed to COVID-19 during the study period, while the 4-week mortality among unvaccinated patients was nearly 15% (8/56). CONCLUSIONS: In this cohort of vaccinated LT patients who developed breakthrough COVID-19, the clinical course, risk of complications, and outcomes trended better than unvaccinated patients. However, universal involvement of the allograft demonstrates the continued vulnerability of these patients to significant sequelae from COVID-19. Future studies may evaluate the incremental protection of vaccination after the completion of the third dose of mRNA vaccines among LT patients.

Characteristics and outcomes among patients with community-acquired respiratory virus infections during the first year after lung transplantation.

BACKGROUND: The current study describes the spectrum of community-acquired respiratory infections (CARV) during the first year after lung transplantation (LT). Additionally, we elucidate variables associated with CARV, management strategies utilized, and impact on early and late outcomes. METHODS: This was a retrospective study among patients transplanted between 2012 and 2015 (n = 255, mean age 55.6 ± 13.5 years, M: F 152:103). The diagnosis of CARV was based on the multiplex PCR on nasopharyngeal swab samples. Baseline characteristics, post-transplant variables, and outcomes were compared among patients with and without CARV. RESULTS: Eighty CARV infections developed among a quarter of the study group (n = 62, 24.3%). Rhinovirus/enterovirus was the most commonly isolated CARV (n = 24) followed by coronavirus (n = 17) and RSV (n = 9). A significant proportion of episodes (43.8%) required hospitalization. The use of nasal corticosteroids and left single LT was independently associated with an increased risk of CARV. CARV infections did not impact the lung functions during the first year or the CLAD-free survival at 3 years. CONCLUSIONS: There is a significant burden of CARV infections during the first year after LT. The use of nasal corticosteroids may increase the risk of CARV infection. CARV infections did not impact outcomes.

Characteristics and outcomes among lung transplant patients with respiratory syncytial virus infection.

BACKGROUND: To describe characteristics and outcomes among lung transplantation (LT) patients with respiratory syncytial virus (RSV) infection and elucidate the predictors of 1-year survival after RSV infection. METHODS: This was a retrospective chart review study among LT patients with RSV infection between 2013 and 2018 (90 episodes among 87 patients; mean age 56.3 ± 13.1 years, M:F 52:35). A contemporaneous control group consisting of LT patients without RSV infection (n = 183) was included. One-year survival after the RSV infection was the primary endpoint. RESULTS: Median time from LT to RSV infection was 30 (1-155) months. Before RSV infection, the median decline in forced vital capacity (FVC) was 9.7 cc (-17.8 to 83 cc) or 0.29% (-1.4% to 4.6%) per month, while the forced expiratory volume (FEV1 ) decline was 7.5 cc (-8.8 to 58 cc) or 0.3% (-0.57% to 4.3%) per month with no statistically significant change after RSV infection. One-year survival among patients with RSV infection was 86.2% (75/87). Pre-infection diagnosis of chronic lung allograft dysfunction (CLAD; adjusted HR: 4.29, 1.08-17.0; P = .038) and FVC or FEV1 decline >10% during 6 months post infection (adjusted HR: 35.1, 3.26-377.1; P = .003) were independently associated with worse survival. On propensity score matched analysis, RSV infection was not associated with worse post-transplant survival (HR with 95% CI: 0.79, 0.47-1.34; P = .38). CONCLUSIONS: A majority of LT patients in the current cohort did not experience an alteration in the trajectory of FVC or FEV1 decline after developing RSV infection, and their post-transplant survival was not adversely impacted. Established CLAD at the time of RSV infection and post infection >10% decline in FVC or FEV1 are independently associated with worse survival after RSV infection.

Post-infection pulmonary sequelae after COVID-19 among patients with lung transplantation.

BACKGROUND: There is limited data on outcomes among lung transplant (LT) patients who survive Coronavirus disease 2019 (COVID-19). METHODS: Any single or bilateral LT patients who tested positive for SARS-CoV-2 between March 1, 2020, to February 15, 2021 (n = 54) and survived the acute illness were included (final n = 44). Each patient completed at least 3 months of follow-up (median: 4.5; range 3-12 months) after their index hospitalization for COVID-19. The primary endpoint was a significant loss of lung functions (defined as > 10% decline in forced vital capacity (FVC) or forced expiratory volume in 1 s (FEV1 ) on two spirometries, at least 3 weeks apart compared to the pre-infection baseline). RESULTS: A majority of the COVID-19 survivors had persistent parenchymal opacities (n = 29, 65.9%) on post-infection CT chest. Patients had significantly impaired functional status, with the majority reporting residual disabilities (Karnofsky performance scale score of 70% or worse; n = 32, 72.7%). A significant loss of lung function was observed among 18 patients (40.9%). Three patients met the criteria for new chronic lung allograft dysfunction (CLAD) following COVID-19 (5.6%), with all three demonstrating restrictive allograft syndrome phenotype. An absolute lymphocyte count < 0.6 × 103 /dl and ferritin > 150 ng/ml at the time of hospital discharge was independently associated with significant lung function loss. CONCLUSIONS: A significant proportion of COVID-19 survivors suffer persistent allograft injury. Low absolute lymphocyte counts (ALC) and elevated ferritin levels at the conclusion of the hospital course may provide useful prognostic information and form the basis of a customized strategy for ongoing monitoring and management of allograft dysfunction. TWEET: Twitter handle: @AmitBangaMD Lung transplant patients who survive COVID-19 suffer significant morbidity with persistent pulmonary opacities, loss of lung functions, and functional deficits. Residual elevation of the inflammatory markers is predictive.

Outpatient management of Post-COVID syndrome - single center experience.

BACKGROUND: COVID patients continue to experience unremitting symptoms that extend far beyond the initial illness. While there is rapid accumulation of data on acute COVID treatment in hospitalized patients, little is known regarding post-COVID management. OBJECTIVES: To describe our center's experience treating post-COVID sub-syndromes encountered in Post-COVID Lung Clinic. METHODS: We retrospectively reviewed data on 98 post-COVID patients evaluated in our clinic between 07/01/2020-12/31/2022. We encountered three distinct post-COVID subtypes: 1) respiratory complaints associated with increased O2 requirements and abnormal CT findings (post-COVID interstitial lung disease [ILD]), 2) respiratory complaints associated with tachycardia (post-COVID dyspnea-tachycardia syndrome [DTS]). Post-COVID ILD patients (n = 28) received steroids in combination with cell cycle inhibitor (mycophenolate mofetil-MMF). Post-COVID DTS patients (n = 16) were treated with metoprolol. 3) A third, undifferentiated group presented with mild respiratory complaints and normal spirometry (n = 17) and was followed in clinic without initiation of a specific treatment. RESULTS: In treated post-COVID ILD patients, mean oxygen requirements at rest (1.96 ± 1.79 L/NC) decreased to 0.89 ± 1.29 L/NC at 6 months follow-up, p = 0.005. In patients with post-COVID DTS, mean heart rate at rest decreased (98 ± 15 bpm to 79 ± 11 bpm) at 6 months follow-up, p = 0.023. 60 % of patients reported an improvement in exertional dyspnea. CONCLUSIONS: Our descriptive study presents a single center outpatient COVID-19 clinic experience. We encountered 3 post-COVID sub-syndromes and describe their treatments: post-COVID interstitial lung disease [ILD] treated with a novel regimen of MMF and steroids, post COVID dyspnea-tachycardia syndrome [DTS] treated with metoprolol, and a third subgroup with mild undifferentiated symptoms without specific treatment.

A Case Report of Breakthrough Infections With 2 SARS-CoV-2 Variants in a Lung Transplant Patient.

A lung transplant (LT) patient developed 2 distinct episodes of COVID-19, confirmed by whole-genome sequencing, which was caused by the Delta, and then followed 6 weeks later, by the Omicron variant. The clinical course with Omicron was more severe, leading us to speculate that Omicron may not be any milder among LT patients. We discuss the potential mechanisms behind the Omicron not being any milder among LT patients and emphasize the need for outcomes data among these patients. Until such data become available, it may be prudent to maintain clinical equipoise as regards the relative virulence of the newer variants among LT patients.

COVID-19 Vaccination is Associated With Favorable Outcomes Among Lung Transplant Patients With Breakthrough Infections.

BACKGROUND: There are limited data regarding the clinical efficacy of COVID-19 vaccines among lung transplant (LT) patients. METHODS: We included all LT patients diagnosed with COVID-19 between March 1, 2020, and December 10, 2021 (n = 84; median age 55, range, 20-73 years; males 65.5%). The study group was divided into 3 groups based on the vaccination status (patients who did not complete the primary series for any of the vaccines: n = 58; those with 2 doses of messenger RNA (mRNA) or 1 dose of the adenoviral vector vaccine, vaccinated group: n = 16; those with at least 1 additional dose beyond the primary series, boosted group: n = 10). RESULTS: Pulmonary parenchymal involvement on chest computed tomography scan was less common among the boosted group (P = .009). The proportion of patients with new or worsening respiratory failure was significantly lower among the vaccinated and boosted groups and these patients were significantly more likely to achieve the composite endpoint of oxygen-dependence free survival (P = .02). On multivariate logistic regression analysis, higher body mass index, restrictive lung disease as the transplant indication, and preinfection chronic lung allograft dysfunction were independently associated with acute or acute on chronic respiratory failure while being on therapeutic dose anticoagulation and having received the booster dose had a protective effect. CONCLUSION: COVID-19 vaccines appear to have several favorable effects among LT patients with breakthrough infections including lower likelihood of allograft involvement on imaging (among boosted patients), need of hospitalization, and complications such as new or worsening respiratory failure.

ECMO Long Haulers: A Distinct Phenotype of COVID-19-Associated ARDS With Implications for Lung Transplant Candidacy.

BACKGROUND: Studies indicate that the recovery from coronavirus disease 2019 (COVID-19)-associated acute respiratory distress syndrome may be slower than other viral pneumonia. There are limited data to guide decisions among patients who need extracorporeal membrane oxygenation (ECMO) support, especially the expected time of recovery and considering lung transplantation (LT). METHODS: This was a retrospective chart review of patients with COVID-19-associated acute respiratory distress syndrome placed on ECMO between March 1, 2020, and September 15, 2021 (n = 20; median age, 44 y; range, 22-62 y; male:female, 15:5). We contrasted the baseline variables and clinical course of patients with and without the need for ECMO support >30 d (ECMO long haulers, n = 10). RESULTS: Ten patients met the criteria for ECMO long haulers (median duration of ECMO, 86 d; range, 42-201 d). The long haulers were healthier at baseline with fewer comorbidities but had worse pulmonary compliance and higher partial pressure of CO2. They had a significantly higher number of membrane oxygenator failures, changes to their cannulation sites, and suffer more complications on ECMO. One of the long hauler was bridged to LT while another 6 patients recovered and were discharged. Overall survival was better among the ECMO long haulers (70% versus 20%; 9.3, 1.2-73; P = 0.03). CONCLUSIONS: Despite worse pulmonary physiology, frequent complications, and a tortuous hospital course that may appear to portend a poor prognosis, ECMO long haulers have the potential to recover and be weaned off ECMO without the need for LT. A customized approach comprising a more conservative timeline for the consideration of LT may be prudent among these patients.

Clinical characteristics, management practices, and outcomes among lung transplant patients with COVID-19.

BACKGROUND: There are limited data on management strategies and outcomes among lung transplant (LT) patients with Coronavirus disease 2019 (COVID-19). We implemented management protocols based on the best available evidence and consensus among multidisciplinary teams. The current study reports our experience and outcomes using this protocol-based management strategy. METHODS: We included single or bilateral LT patients who tested positive for SARS-CoV-2 on nasopharyngeal swab between March 1, 2020, to December 15, 2020 (n = 25; median age: 60, range 20-73 years; M: F 17:8). A group of patients with Respiratory Syncytial Virus (RSV) infection during 2016-18 were included to serve as a comparator group (n = 36). RESULTS: As compared to RSV, patients with COVID-19 were more likely to present with constitutional symptoms, spirometric decline, pulmonary opacities, new or worsening respiratory failure, and need for ventilator support. Patients with SARS-CoV-2 infection were less likely to receive a multimodality treatment strategy, and they experienced worse post-infection lung function loss, functional decline, and three-month survival. A significant proportion of patients with COVID-19 needed readmission for worsening allograft function (36.4%), and chronic kidney disease at initial presentation was associated with this complication. Lower pre-morbid FEV1 appeared to increase the risk of new or worsening respiratory failure, which was associated with worse outcomes. Overall hospital survival was 88% (n = 22). Follow-up data was available for all discharged patients (median: 43.5 days, range 15-287 days). A majority had persistent radiological opacities (19/22, 86.4%), with nearly half of the patients with available post-COVID-19 spirometry showing > 10% loss in lung function (6/13, median loss: 14.5%, range 10%-31%). CONCLUSIONS: Despite similar demographic characteristics and predispositions, LT patients with COVID-19 are sicker and experience worse outcomes as compared to RSV. Despite the availability of newer therapeutic agents, COVID-19 continues to be associated with significant morbidity and mortality.

Significance of Best Spirometry in the First Year After Bilateral Lung Transplantation: Association With 3-Year Outcomes.

BACKGROUND: Spirometry is the cornerstone of monitoring allograft function after lung transplantation (LT). We sought to determine the association of variables on best spirometry during the first year after bilateral LT with 3-year posttransplant survival. METHODS: We reviewed charts of patients who survived at least 3 months after bilateral LT (n = 157; age ± SD: 54 ± 13 y, male:female = 91:66). Best spirometry was calculated as the average of 2 highest measurements at least 3 weeks apart during the first year. Airway obstruction was defined as forced expiratory volume in 1-second (FEV1)/forced vital capacity (FVC) ratio <0.7. Survival was compared based on the ventilatory defect and among groups based on the best FEV1 and FVC measurements (>80%, 60%-80%, and <60% predicted). Primary outcome was 3-year survival. RESULTS: Overall, 3-year survival was 67% (n = 106). Obstructive defect was uncommon (7%) and did not have an association with 3-year survival (72% versus 67%, P = 0.7). Although one-half patients achieved an FVC>80% predicted (49%), 1 in 5 (19%) remained below 60% predicted. Irrespective of the type of ventilatory defect, survival worsened as the best FVC (% predicted) got lower (>80: 80.8%; 60-80: 63.3%; <60: 40%; P < 0.001). On multivariate logistic regression analysis, after adjusting for age, gender, transplant indication, and annual bronchoscopy findings, best FVC (% predicted) during the first year after LT was independently associated with 3-year survival. CONCLUSIONS: A significant proportion of bilateral LT patients do not achieve FVC>80% predicted. Although the type of ventilatory defect on best spirometry does not predict survival, failure to achieve FVC>80% predicted during the first year was independently associated with 3-year mortality.

Impact of bedside bronchoscopy in critically ill lung transplant recipients.

BACKGROUND: Over 32,000 lung transplants have been performed worldwide for a variety of end-stage lung diseases (http://www.ishlt.org/). Flexible bronchoscopy (FB) is frequently used as a bedside-tool for diagnosis and management of respiratory failure among critically ill lung transplant recipients (LTRs). We study the indications, results, therapeutic impact, and complications of FB in LTRs admitted to medical intensive care unit (MICU). METHODS: Retrospective chart review was performed for all critically ill LTRs undergoing FB while admitted to MICU at the Cleveland Clinic Foundation between 2009 and 2011. ICD-9 codes for bronchoscopy were used to identify patients. The procedures were categorized as: (i) airway examination and interventions, (ii) microbiological, and (iii) histopathologic diagnosis. SAS version 9.2 was used for analysis. RESULTS: A cohort of 76 LTRs accounted for 93 hospital admissions, 101 MICU admissions, and 129 bronchoscopies. FB was helpful in evaluation and management of airway complications [secretion clearance (18% bronchoscopy procedures), stenosis/dehiscence (8% patients)] and optimizing management of lower respiratory tract infections. Isolation of resistant gram-negative organisms, community-acquired respiratory viruses, and fungi commonly led to modification in antimicrobial therapy (35% microbiological samples). Nonspecific finding of acute lung injury was the most commonly seen histopathology (70%) on transbronchial biopsy. Twenty percent (4/20) of transbronchial biopsies showed acute cellular rejection, with 1 episode contributing to respiratory failure. Occasional hypoxia and hypotension, but no deaths, were noted due to FB during the ICU admission. CONCLUSIONS: Use of FB modified clinical management in one third of airway evaluation and microbiological sampling procedures for critically ill LTRs. No fatalities were attributed to bronchoscopy in this critically ill population.

A survey of practices of pulmonary function interpretation in laboratories in Northeast Ohio.

BACKGROUND: Because many different reference equations are available for pulmonary function testing (PFT), and because different interpretive strategies could affect the interpretation of results, we assessed the variation in practice among 17 PFT laboratories. METHODS: PFT laboratory directors/supervisors in 17 hospitals (near Cleveland, Ohio) were surveyed between September 15, 2010, and January 5, 2011. The survey assessed the features of the laboratory, including equipment used, types of tests offered, volume of testing, reference equations used, and interpretive strategies employed (eg, how normal was determined, how tests were actually read, and so forth). RESULTS: Responses were received from all 17 laboratories and were verified using submitted sample PFT reports. The daily median number of tests performed and patients evaluated were 16 and six, respectively. Great variation was observed not only in the choice of reference equations for spirometry, but also in the criteria used to define airflow obstruction. Great variation was also observed in the reference equations used for lung volumes and diffusing capacity, as well as in the criteria used to define physiologic derangements such as restriction, hyperinflation, air trapping, and impaired diffusing capacity. Only three of the 17 laboratories reported and used the "lower limit of normal" to define PFT abnormality. CONCLUSIONS: This survey demonstrated substantial variation in PFT laboratory practices, including the choice of reference equations, the criteria used to define abnormality, and the strategies for interpreting tests. The degree of variation raises concern about the consistency of the interpretation of results among laboratories and emphasizes the value of compliance with official guidelines to drive standardization.