Systemic corticosteroids for outpatient respiratory viral infections in lung transplant recipients.

INTRODUCTION: Respiratory viral infections (RVI) in lung transplant recipients (LTR) have variably been associated with rejection and chronic lung allograft dysfunction. Our center has used systemic corticosteroids to treat outpatient RVI in some cases, but evidence is limited. We reviewed all adult LTR diagnosed with outpatient RVI January 2017 to December 2019. The primary outcome was recovery of lung function (forced expiratory volume in 1 s [FEV1]) at next stable visit between 1 and 12 months postinfection, expressed as a ratio over stable preinfection FEV1 (FEV1 recovery ratio). METHODS: We identified 100 adult LTR with outpatient RVI diagnoses eligible for study, 36% of whom received corticosteroids. We modelled the adjusted association between corticosteroid use and FEV1 recovery ratio using linear regression. RESULTS: Steroid-treated patients had a lower FEV1 presentation ratio (0.92 vs. 1.04, p = .0070) and were more likely to have chronic lung allograft dysfunction at time of infection (25% vs. 5%, p = .0077). Mean FEV1 recovery ratio was 1.02 (SD 0.19) with no association with corticosteroid therapy via multivariable linear regression (p = .5888). CONCLUSIONS: Steroid treatment was not associated with FEV1 recovery. This suggests corticosteroids may not have a role in the management of RVI in this population.

Association Between the Pulmonary Artery Pulsatility Index and Prognosis in Pulmonary Arterial Hypertension: A Multicentre Study.

Background: Risk stratification is fundamental in the management of pulmonary arterial hypertension (PAH). Pulmonary artery pulsatility index (PAPi), defined as pulmonary arterial pulse pressure divided by right atrial pressure (RAP), is a hemodynamic index shown to predict acute right ventricular (RV) dysfunction in several settings. Our objective was to test the prognostic utility of PAPi in a diverse multicentre cohort of patients with PAH. Methods: A multicentre retrospective cohort study of consecutive adult patients with a new diagnosis of PAH on right heart catheterization between January 2016 and December 2020 was undertaken across 4 major centres in Canada. Hemodynamic data, clinical data, and outcomes were collected. The association of PAPi and other hemodynamic variables with mortality was assessed by receiver-operating characteristic curves and Cox proportional hazards modeling. Results: We identified 590 patients with a mean age of 61.4 ± 15.5 years, with 66.3% being female. A low PAPi (defined as < 5.3) was associated with higher mortality at 1 year: 10.2% vs 5.2% (P = 0.02). In a multivariable model including age, sex, body mass index, and functional class, a low PAPi was associated with mortality at 1 year (area under the curveof 0.64 (95% confidence interval 0.55-0.74). However, high RAP (> 8 mm Hg) was similarly predictive of mortality, with an area under the curve of 0.65. Conclusion: PAPi was associated with mortality in a large incident PAH cohort. However, the discriminative value of PAPi was not higher than that of RAP alone.

Contexte: La stratification des risques est fondamentale dans la prise en charge de l'hypertension artérielle pulmonaire (HTAP). L'indice de pulsatilité des artères pulmonaires (iPAP), défini comme la pression différentielle dans les artères pulmonaires divisée par la pression auriculaire droite (PAD), est un indice hémodynamique qui s'est révélé prédictif d'une dysfonction ventriculaire droite (VD) aiguë dans plusieurs situations. Notre objectif était d'évaluer l'utilité pronostique de l'iPAP dans une cohorte multicentrique diversifiée de patients atteints d'HTAP. Méthodologie: Une étude de cohorte multicentrique rétrospective de patients adultes consécutifs atteints d'une HTAP nouvellement diagnostiquée par cathétérisme cardiaque droit entre janvier 2016 et décembre 2020 a été effectuée dans quatre grands centres au Canada. Les données hémodynamiques, les données cliniques et les résultats ont été recueillis. La corrélation de l'iPAP et d'autres va-riables hémodynamiques avec la mortalité a été évaluée par les courbes caractéristiques opérationnelles du receveur et des modèles à risques proportionnels de Cox. Résultats: Nous avons recensé 590 patients dont l'âge moyen était de 61,4 ± 15,5 ans; la proportion de femmes était de 66,3 %. Un faible iPAP (défini comme une valeur < 5,3) a été associé à une hausse de la mortalité à 1 an : 10,2 % contre 5,2 % (p= 0,02). Dans un modèle multivarié comprenant l'âge, le sexe, l'indice de masse corporelle et la classe fonctionnelle, un faible iPAP a été associé à la mortalité à 1 an (aire sous la courbe de 0,64 [intervalle de confiance à 95 %; de 0,55 à 0,74]). Cependant, une PAD élevée (> 8 mmHg) a aussi été un facteur prédictif de mortalité, l'aire sous la courbe étant de 0,65. Conclusions: L'iPAP a été associé à la mortalité dans une vaste cohorte de patients atteints d'une HTAP. Toutefois, la valeur discriminante de l'iPAP n'a pas été supérieure à celle de la PAD seule.

Relative Lung Perfusion on Ventilation-Perfusion Scans After Double Lung Transplant.

BACKGROUND: Pulmonary blood flow can be assessed on ventilation-perfusion (VQ) scan with relative lung perfusion, with a 55% to 45% (or 10%) right-to-left differential considered normal. We hypothesized that wide perfusion differential on routine VQ studies at 3 mo posttransplant would be associated with an increased risk of death or retransplantation, chronic lung allograft (CLAD), and baseline lung allograft dysfunction. METHODS: We conducted a retrospective cohort study on all patients who underwent double-lung transplant in our program between 2005 and 2016, identifying patients with a wide perfusion differential of >10% on a 3-mo VQ scan. We used Kaplan-Meier estimates and proportional hazards models to assess the association between perfusion differential and time to death or retransplant and time to CLAD onset. We used correlation and linear regression to assess the relationship with lung function at time of scan and with baseline lung allograft dysfunction. RESULTS: Of 340 patients who met inclusion criteria, 169 (49%) had a relative perfusion differential of ≥ 10% on a 3-mo VQ scan. Patients with increased perfusion differential had increased risk of death or retransplantation ( P = 0.011) and CLAD onset ( P = 0.012) after adjustment for other radiographic/endoscopic abnormalities. Increased perfusion differential was associated with lower lung function at time of scan. CONCLUSIONS: Wide lung perfusion differential was common after lung transplant in our cohort and associated with increased risk of death, poor lung function, and CLAD onset. The nature of this abnormality and its use as a predictor of future risk warrant further investigation.

Management of Pulmonary Arterial Hypertension.

Pulmonary arterial hypertension (PAH) is a rare pulmonary vascular disease characterized by progressive pulmonary arterial remodeling, increased pulmonary vascular resistance, right ventricular dysfunction, and reduced survival. Effective therapies have been developed that target three pathobiologic pathways in PAH: nitric oxide, endothelin-1, and prostacyclin. Approved therapies for PAH include phosphodiesterase type-5 inhibitors, soluble guanylate cyclase stimulators, endothelin receptor antagonists, prostacyclin analogs, and prostacyclin receptor agonists. Management of PAH in the modern era incorporates multidimensional risk assessment to guide the use of these medications. For patients with PAH and without significant comorbidities, current guidelines recommend two oral medications (phosphodiesterase type-5 inhibitor and endothelin receptor antagonist) for low- and intermediate-risk patients, with triple therapy including a parenteral prostacyclin to be considered in those at high or intermediate-high risk. Combination therapy may be poorly tolerated and less effective in patients with PAH and cardiopulmonary comorbidities. Thus, a single-agent approach with individualized decisions to add-on other PAH therapies is recommended in older patients and those with significant comorbid conditions. Management of PAH is best performed in multidisciplinary teams located in experienced centers. Other core pillars of PAH management include supportive and adjunctive treatments including oxygen, diuretics, rehabilitation, and anticoagulation in certain patients. Patients with PAH who progress despite optimal treatment or who are refractory to best medical care should be referred for lung transplantation, if eligible. Despite considerable progress, PAH is often fatal and new therapies that reverse the disease and improve outcomes are desperately needed.

Safety of Crossing Donor-specific Antibodies in Lung Transplantation.

BACKGROUND: Donor-specific antibodies (DSAs) have been associated with antibody-mediated rejection, chronic lung allograft dysfunction (CLAD), and increased mortality in lung transplant recipients. Our center performs transplants in the presence of DSA, and we sought to evaluate the safety of this practice with respect to graft loss, CLAD onset, and primary graft dysfunction (PGD). METHODS: We reviewed recipients transplanted from 2010 to 2017, classifying them as DSA positive (DSA + ) or negative. We used Kaplan-Meier estimation to test the association between DSA status and time to death or retransplant and time to CLAD onset. We further tested associations with severe PGD and rejection in the first year using logistic regression and Fisher exact testing. RESULTS: Three hundred thirteen patients met inclusion criteria, 30 (10%) of whom were DSA + . DSA + patients were more likely to be female, bridged to transplant, and receive induction therapy. There was no association between DSA status and time to death or retransplant (log rank P = 0.581) nor death-censored time to CLAD onset (log rank P = 0.278), but DSA + patients were at increased risk of severe PGD (odds ratio 2.88; 95% confidence interval, 1.10-7.29; P = 0.031) and more frequent antibody-mediated rejection in the first posttransplant year. CONCLUSIONS: Crossing DSA at time of lung transplant was not associated with an increased risk of death or CLAD in our cohort, but patients developed severe PGD and antibody-mediated rejection more frequently. However, these risks are likely manageable when balanced against the benefits of expanded access for sensitized candidates.

Reliability and validity of the post COVID-19 condition stigma questionnaire: A prospective cohort study.

Background: Many of the 10-20% percent of COVID-19 survivors who develop Post COVID-19 Condition (PCC, or Long COVID) describe experiences suggestive of stigmatization, a known social determinant of health. Our objective was to develop an instrument, the Post COVID-19 Condition Stigma Questionnaire (PCCSQ), with which to quantify and characterise PCC-related stigma. Methods: We conducted a prospective cohort study to assess the reliability and validity of the PCCSQ. Patients referred to our Post COVID-19 Clinic in the Canadian City of Edmonton, Alberta between May 29, 2021 and May 24, 2022 who met inclusion criteria (attending an academic post COVID-19 clinic; age ≥18 years; persistent symptoms and impairment at ≥ 12 weeks since PCR positive acute COVID-19 infection; English-speaking; internet access; consenting) were invited to complete online questionnaires, including the PCCSQ. Analyses were conducted to estimate the instrument's reliability, construct validity, and association with relevant instruments and defined health outcomes. Findings: Of the 198 patients invited, 145 (73%) met inclusion criteria and completed usable questionnaires. Total Stigma Score (TSS) on the PCCSQ ranged from 40 to 174/200. The mean (SD) was 103.9 (31.3). Cronbach's alpha was 0.97. Test-retest reliability was 0.92. Factor analysis supported a 6-factor latent construct. Subtest reliabilities were >0.75. Individuals reporting increased TSS occurred across all demographic groups. Increased risk categories included women, white ethnicity, and limited educational opportunities. TSS was positively correlated with symptoms, depression, anxiety, loneliness, reduced self-esteem, thoughts of self-harm, post-COVID functional status, frailty, EQ5D5L score, and number of ED visits. It was negatively correlated with perceived social support, 6-min walk distance, and EQ5D5L global rating. Stigma scores were significantly increased among participants reporting employment status as disabled. Interpretation: Our findings suggested that the PCCSQ is a valid, reliable tool with which to estimate PCC-related stigma. It allows for the identification of patients reporting increased stigma and offers insights into their experiences. Funding: The Edmonton Post COVID-19 Clinic is supported by the University of Alberta and Alberta Health Services. No additional sources of funding were involved in the execution of this research study.

Persistent dyspnea after COVID-19 is not related to cardiopulmonary impairment; a cross-sectional study of persistently dyspneic COVID-19, non-dyspneic COVID-19 and controls.

Background: Up to 53% of individuals who had mild COVID-19 experience symptoms for >3-month following infection (Long-CoV). Dyspnea is reported in 60% of Long-CoV cases and may be secondary to impaired exercise capacity (VO2peak) as a result of pulmonary, pulmonary vascular, or cardiac insult. This study examined whether cardiopulmonary mechanisms could explain exertional dyspnea in Long-CoV. Methods: A cross-sectional study of participants with Long-CoV (n = 28, age 40 ± 11 years, 214 ± 85 days post-infection) and age- sex- and body mass index-matched COVID-19 naïve controls (Con, n = 24, age 41 ± 12 years) and participants fully recovered from COVID-19 (ns-CoV, n = 14, age 37 ± 9 years, 198 ± 89 days post-infection) was conducted. Participants self-reported symptoms and baseline dyspnea (modified Medical Research Council, mMRC, dyspnea grade), then underwent a comprehensive pulmonary function test, cardiopulmonary exercise test, exercise pulmonary diffusing capacity measurement, and rest and exercise echocardiography. Results: VO2peak, pulmonary function and cardiac/pulmonary vascular parameters were not impaired in Long- or ns-CoV compared to normative values (VO2peak: 106 ± 25 and 107 ± 25%predicted, respectively) and cardiopulmonary responses to exercise were otherwise normal. When Long-CoV were stratified by clinical dyspnea severity (mMRC = 0 vs mMRC≥1), there were no between-group differences in VO2peak. During submaximal exercise, dyspnea and ventilation were increased in the mMRC≥1 group, despite normal operating lung volumes, arterial saturation, diffusing capacity and indicators of pulmonary vascular pressures. Interpretation: Persistent dyspnea after COVID-19 was not associated with overt cardiopulmonary impairment or exercise intolerance. Interventions focusing on dyspnea management may be appropriate for Long-CoV patients who report dyspnea without cardiopulmonary impairment.

Pre-transplant malignancy is associated with increased risk of de novo malignancy post-lung transplantation.

BACKGROUND: At least 20% of lung transplant recipients will be diagnosed with a malignancy within 5 years of transplant. Transplant candidates with a history of pre-transplant malignancy must meet remission criteria before listing to minimize the risk of recurrence, however these patients may have an intrinsic predisposition to developing subsequent cancers which can be amplified by immunosuppression. We assessed whether pre-transplant malignancy was associated with an increased risk of developing malignancy of any type after lung transplant. METHODS: We conducted a single centre retrospective cohort study of patients undergoing lung transplant between January 2006 and December 2017. We used a proportional hazards regression model to test whether preTM was associated with the risk of developing one or more postTM after lung transplant, adjusted for known cancer risk factors. RESULTS: 497 adult patients underwent lung transplantation during the study period and 26 (5.2%) had pre-transplant malignancies. Out of 29 pre-transplant cancer diagnoses, prostate cancer was the most common (17.2%), followed by breast cancer and basal cell carcinoma (13.8% each). 108 (22%) patients developed post-transplant malignancy with a total of 328 cancer diagnoses. The most common post-transplant malignancy was non-melanoma skin cancer (86.3%), followed by solid organ cancers (7.6%). Pre-transplant malignancy was associated with an adjusted HR of 3.24 (95% CI 1.71 to 6.14, p < 0.001) for the development of post-transplant malignancy. Recurrence of the pre-transplant malignancy only occurred in 3 patients post-transplant. CONCLUSIONS: History of pre-transplant malignancy was associated with a more than three times likelihood of development of a post-transplant malignancy compared to recipients without a previous history of cancer, the majority being unrelated to the initial malignancy. These findings highlight the importance of frequent cancer surveillance in lung transplant recipients, especially in those with a history of pre-transplant malignancy.

Mismatched perfusion defects on routine ventilation-perfusion scans after lung transplantation.

BACKGROUND: Incidental pulmonary embolism (PE) is a challenging entity with unclear treatment implications. Our program performs routine ventilation-perfusion (VQ) scans at 3-months post-transplant to establish airway and vascular function. We sought to determine the prevalence and prognostic implications of mismatched perfusion defects (MMPD) found on these studies, hypothesizing they would be associated with a benign prognosis. METHODS: We studied VQ scans obtained routinely at 3-months post-transplant from double lung transplant recipients 2005-2016 for studies with MMPD interpreted as high or intermediate probability for PE. We tested the relationship between MMPD and 1-year survival via chi square testing, overall survival via Kaplan Meier analysis with log rank testing and peak forced expiratory volume in 1 second (FEV1) percent predicted via t-testing. RESULTS: Three hundred and seventy-three patients met inclusion criteria, of whom 35 (9%) had VQ scans with MMPDs interpreted by radiologists as high or intermediate probability for PE. Baseline recipient and donor characteristics were similar between groups. Seven patients (20%) in the MMPD group were treated with therapeutic anticoagulation. Patients with MMPD had similar 1-year survival (100% vs. 98%, P = 1.00), overall survival (log rank P = .90) and peak FEV1% predicted (94% [SD 20%] vs. 92% [SD 21%]; P = .58). Anticoagulation did not affect these relationships. CONCLUSION: Mismatched perfusion defects on routine post-transplant VQ scan were not associated with a difference in survival or lung function. A conservative approach to these changes may be a viable option in the absence of other anticoagulation indications.

Upfront riociguat and ambrisentan combination therapy for newly diagnosed pulmonary arterial hypertension: A prospective open-label trial.

BACKGROUND: Initial combination therapy with an endothelin receptor antagonist (ERA) and riociguat in pulmonary arterial hypertension (PAH) has limited supporting data. METHODS: We performed a prospective, single-arm, open-label trial of riociguat, and ambrisentan for incident PAH patients in functional class III. The primary endpoint was pulmonary vascular resistance (PVR) at 4-months. RESULTS: Twenty patients (59 ± 13 years old, 85% female) enrolled and 1 died before their 4-month follow-up. Fifteen patients completed a 4-month and 13 completed the 12-month follow-up. At 4-months PVR decreased 54% with an absolute change of -5.8 Wood units (95% CI -4.0; -7.5, p < 0.001). Other hemodynamic variables and risk scores also improved. Six patients discontinued riociguat and 8 discontinued ambrisentan, with 5 (25%) discontinuing both. CONCLUSIONS: These results do not support the routine use of riociguat plus ambrisentan in initial regimens. Future studies are needed to compare this strategy with phosphodiesterase-5 inhibitors and an ERA with respect to tolerability and long-term outcomes.

Mortality trends in pulmonary arterial hypertension in Canada: a temporal analysis of survival per ESC/ERS guideline era.

BACKGROUND: The evolution in pulmonary arterial hypertension (PAH) management has been summarised in three iterations of the European Society of Cardiology/European Respiratory Society (ESC/ERS) guidelines. No study has assessed whether changes in management, as reflected in the changing guidelines, has translated to improved long-term survival in PAH. METHODS: We performed a mixed retrospective/prospective analysis of treatment-naïve, incident PAH patients (n=392) diagnosed at three major centres in Canada from 2009 to 2021. Patients were divided into two groups based on their diagnosis date and in accordance with the 2009 and 2015 ESC/ERS guideline iterations. Overall survival was assessed based on date of diagnosis and initial treatment strategy (i.e. monotherapy versus combination therapy). RESULTS: There was a shift towards more aggressive upfront management with combination therapy in Canada after the publication of the 2015 ESC/ERS guidelines (10.4% and 30.8% in patients from 2009 to 2015 and 36.0% and 57.4% in patients diagnosed after 2015 for baseline and 2-year follow-up, respectively). A key factor associated with combination therapy after 2015 was higher pulmonary vascular resistance (p=0.009). The 1-, 3- and 5-year survival rates in Canada were 89.2%, 75.6% and 56.0%, respectively. Despite changes in management, there was no improvement in long-term survival before and after publication of the 2015 ESC/ERS guidelines (p=0.53). CONCLUSIONS: There was an increase in the use of initial and sequential combination therapy in Canada after publication of the 2015 ESC/ERS guidelines, which was not associated with improved long-term survival. These data highlight the continued difficulties of managing this aggressive pulmonary disease in an era without a cure.

COVID-19 hospitalization is associated with pulmonary/diffusion abnormalities but not post-acute sequelae of COVID-19 severity.

Coronavirus disease-19 (COVID-19) has resulted in much acute morbidity and mortality worldwide. There is now a growing recognition of the post-acute sequela of COVID-19, termed long COVID. However, the risk factors contributing to this condition remain unclear. Here, we address the growing controversy in the literature of whether hospitalization is a risk factor for long COVID. We found that hospitalization is associated with worse pulmonary restriction and reduction in diffusion capacity at 3 months post-infection. However, the impact on mental health, functional and quality of life is equally severe in those who have and have not been hospitalized during the acute infection. These findings suggest that hospitalization is a risk factor for pulmonary complications of long COVID but not the overall severity of long COVID.

Successful Long-Term Outcome After Transplantation of Lungs Affected by Smoke Inhalation Injury.

We report a case of a 43-year-old woman who underwent double lung transplantation from a donor with severe airway burns following a house fire. The recipient's lung function and quality of life remain excellent 24 months following transplantation. This case is the first to report successful long-term outcomes in transplantation of lungs affected by smoke inhalation.

ANOTHER syndrome-Familial presentations of progressive lung disease leading to double lung transplantation: A case report and literature review.

Ectodermal dysplasias (EDs) are a heterogeneous rare group of disorders with an incidence at 1/100,000 live births. Currently, there are limited case reports of patients requiring lung transplantation. Here, we report two brothers who present with a constellation of features including alopecia, nail dystrophy, ophthalmic complications, thyroid disease, hypohidrosis, ephelides, enteropathy and recurrent respiratory tract infections, known as ANOTHER syndrome, a rare autosomal recessive variant of ED. Both presented in early childhood with progressive respiratory decline and eventual failure. Chronic respiratory decline was refractory to standard therapy. Both patients required lung transplantation for sequelae of end-stage lung disease. Pathology demonstrated multifocal bronchiectasis with areas of fibrosis and small airway obstruction. ANOTHER syndrome is rare with a paucity of data in the literature. Given the limited therapeutic options available with natural progression towards respiratory failure, lung transplantation may be considered.

Treatment of moderate to severe respiratory COVID-19: a cost-utility analysis.

Despite COVID-19's significant morbidity and mortality, considering cost-effectiveness of pharmacologic treatment strategies for hospitalized patients remains critical to support healthcare resource decisions within budgetary constraints. As such, we calculated the cost-effectiveness of using remdesivir and dexamethasone for moderate to severe COVID-19 respiratory infections using the United States health care system as a representative model. A decision analytic model modelled a base case scenario of a 60-year-old patient admitted to hospital with COVID-19. Patients requiring oxygen were considered moderate severity, and patients with severe COVID-19 required intubation with intensive care. Strategies modelled included giving remdesivir to all patients, remdesivir in only moderate and only severe infections, dexamethasone to all patients, dexamethasone in severe infections, remdesivir in moderate/dexamethasone in severe infections, and best supportive care. Data for the model came from the published literature. The time horizon was 1 year; no discounting was performed due to the short duration. The perspective was of the payer in the United States health care system. Supportive care for moderate/severe COVID-19 cost $11,112.98 with 0.7155 quality adjusted life-year (QALY) obtained. Using dexamethasone for all patients was the most-cost effective with an incremental cost-effectiveness ratio of $980.84/QALY; all remdesivir strategies were more costly and less effective. Probabilistic sensitivity analyses showed dexamethasone for all patients was most cost-effective in 98.3% of scenarios. Dexamethasone for moderate-severe COVID-19 infections was the most cost-effective strategy and would have minimal budget impact. Based on current data, remdesivir is unlikely to be a cost-effective treatment for COVID-19.

Baseline lung allograft dysfunction in primary graft dysfunction survivors after lung transplantation.

BACKGROUND: Primary graft dysfunction (PGD) after lung transplantation has previously been associated with increased risk of death and chronic lung allograft dysfunction (CLAD), but the relationship to baseline lung allograft dysfunction (BLAD), where graft function fails to normalize, is not known. METHODS: We reviewed all double lung transplant recipients transplanted in our program 2004-2016. We defined PGD and CLAD as per recent consensus definitions and BLAD as failure to achieve both FEV1 and FVC ≥80% predicted on 2 consecutive tests ≥3 weeks apart. We used logistic and proportional hazards regression to test the association between severe high-grade PGD (PGD3) with BLAD and CLAD respectively, adjusting for known and identified confounders. RESULTS: 446 patients met inclusion criteria and 76 (17%) developed PGD3 at 48- or 72-h post-transplant. PGD3 occurred more frequently in patients with interstitial lung disease or pulmonary vascular disease, those with higher BMIs and recipients of older donors. PGD3 was associated with more frequent (58% vs. 36%; p = 0.0008) and more severe BLAD (p < 0.0001) and increased BLAD risk in an adjusted model (OR 2.00 [95% CI 1.13-3.60]; p = 0.0182). PGD3 was not associated with CLAD frequency, severity or time to CLAD onset in an adjusted model (HR 1.10 (95% CI 0.64-1.78), p = 0.7226). CONCLUSION: Severe PGD was associated with increased risk and severity of BLAD but not CLAD. The mechanisms via which PGD may mediate baseline function warrant further investigation.

Exertional intolerance and dyspnea with preserved lung function: an emerging long COVID phenotype?

The COVID-19 pandemic has resulted in significant acute morbidity and mortality worldwide. There is now a growing recognition of the longer-term sequelae of this infection, termed "long COVID". However, little is known about this condition. Here, we describe a distinct phenotype seen in a subset of patients with long COVID who have reduced exercise tolerance as measured by the 6 min walk test. They are associated with significant exertional dyspnea, reduced health-related quality of life and poor functional status. However, surprisingly, they do not appear to have any major pulmonary function abnormalities or increased burden of neurologic, musculoskeletal or fatigue symptoms.

Cumulative Deficits Frailty Index Predicts Outcomes for Solid Organ Transplant Candidates.

Despite comprehensive multidisciplinary candidacy assessments to determine appropriateness for solid organ transplantation, limitations persist in identifying candidates at risk of adverse outcomes. Frailty measures may help inform candidacy evaluation. Our main objective was to create a solid organ transplant frailty index (FI), using the cumulative deficits model, from data routinely collected during candidacy assessments. Secondary objectives included creating a social vulnerability index (SVI) from assessment data and evaluating associations between the FI and assessment, waitlist, and posttransplant outcomes. METHODS: In this retrospective cohort study of solid organ transplant candidates from Toronto General Hospital, cumulative deficits FI and SVI were created from data collected during candidacy evaluations for consecutive kidney, heart, liver, and lung transplant candidates. Regression modeling measured associations between the FI and transplant listing, death or removal from the transplant waitlist, and survival after waitlist placement. RESULTS: For 794 patients, 40 variable FI and 10 variable SVI were created (258 lung, 222 kidney, 201 liver, and 113 heart transplant candidates). The FI correlated with assessment outcomes; patients with medical contraindications (mean FI 0.35 ± 0.10) had higher FI scores than those listed (0.29 ± 0.09), P < 0.001. For listed patients, adjusted for age, sex, transplant type, and SVI, higher FI was associated with an increased risk of death (pretransplant or posttransplant) or delisting (hazard ratio 1.03 per 0.01 FI score, 95% confidence interval, 1.01-1.05, P = 0.01). CONCLUSIONS: A cumulative deficits FI can be derived from routine organ transplant candidacy evaluations and may identify candidates at higher risk of adverse outcomes.

Atelectasis in primary graft dysfunction survivors after lung transplantation.

BACKGROUND: Primary graft dysfunction (PGD) is an important contributor to early mortality in lung transplant recipients and is associated with impaired lung function. The radiographic sequelae of PGD on computed tomography (CT) have not been characterized. METHODS: We studied adult double lung transplant recipients from 2010 to 2016 for whom protocol 3-month post-transplant CT scans were available. We assessed CTs for changes including pleural effusions, ground glass opacification, atelectasis, centrilobular nodularity, consolidation, interlobular septal thickening, air trapping and fibrosis, and their relationship to prior post-transplant PGD, future lung function, post-transplant baseline lung allograft dysfunction (BLAD), and chronic lung allograft dysfunction (CLAD). RESULTS: Of 237 patients studied, 50 (21%) developed grade 3 PGD (PGD3) at 48 or 72 h. PGD3 was associated with increased interlobular septal thickening (p = .0389) and atelectasis (p = .0001) at 3 months, but only atelectasis remained associated after correction for multiple testing. Atelectasis severity was associated with lower peak forced expiratory volume in 1 s (FEV1) and increased risk of BLAD (p = .0014) but not with future CLAD onset (p = .7789). CONCLUSIONS: Severe PGD was associated with atelectasis on 3-month post-transplant CT in our cohort. Atelectasis on routine CT may be an intermediary identifiable stage between PGD and future poor lung function.