Oscillometry in Stable Single and Double Lung Allograft Recipients Transplanted for Interstitial Lung Disease: Results of a Multi-Center Australian Study.

Peak spirometry after single lung transplantation (SLTx) for interstitial lung disease (ILD) is lower than after double lung transplantation (DLTx), however the pathophysiologic mechanisms are unclear. We aim to assess respiratory mechanics in SLTx and DLTx for ILD using oscillometry. Spirometry and oscillometry (tremoflo® C-100) were performed in stable SLTx and DLTx recipients in a multi-center study. Resistance (R5, R5-19) and reactance (X5) were compared between LTx recipient groups, matched by age and gender. A model of respiratory impedance using ILD and DLTx data was performed. In total, 45 stable LTx recipients were recruited (SLTx n = 23, DLTx n = 22; males: 87.0% vs. 77.3%; median age 63.0 vs. 63.0 years). Spirometry was significantly lower after SLTx compared with DLTx: %-predicted mean (SD) FEV1 [70.0 (14.5) vs. 93.5 (26.0)%]; FVC [70.5 (16.8) vs. 90.7 (12.8)%], p < 0.01. R5 and R5-19 were similar between groups (p = 0.94 and p = 0.11, respectively) yet X5 was significantly worse after SLTx: median (IQR) X5 [-1.88 (-2.89 to -1.39) vs. -1.22 (-1.87 to -0.86)] cmH2O.s/L], p < 0.01. R5 and X5 measurements from the model were congruent with measurements in SLTx recipients. The similarities in resistance, yet differences in spirometry and reactance between both transplant groups suggest the important contribution of elastic properties to the pathophysiology. Oscillometry may provide further insight into the physiological changes occurring post-LTx.

Case Report: Bilateral Lung Transplantation for Rapidly Progressive Undifferentiated Interstitial Lung Disease-A Cautionary Tale.

Interstitial lung disease is fast becoming one of the most common indications for lung transplantation (LTx); however, LTx for Goodpasture's syndrome with pulmonary involvement has not been previously described in the literature. In this report, we outline the case of a young male with undifferentiated rapidly progressive interstitial lung disease who ultimately received a bilateral sequential LTx after deterioration requiring extracorporeal membrane oxygenation. The original disease soon recurred in the graft, and unfortunately, the patient did not survive. The diagnosis of Goodpasture's syndrome was made postmortem and was not clearly evident on examination of the native explanted tissue, nor was there an elevated titer of antiglomerular basement membrane antibodies during his initial work-up. We hypothesize that the donor and recipient's HLA profile made him more susceptible to aggressive disease. In hindsight, active Goodpasture's disease would have been a contraindication to proceed to transplantation. This case is a cautionary reminder of the high stakes of performing LTx without a certain diagnosis.

Survival after lipiodol escape at embolization for lung transplant chylothorax.

We present imaging of lipiodil escape after thoracic duct embolization for transplant associated chylothorax leading to transient impairment, then resolution.

Airway oscillometry parameters in baseline lung allograft dysfunction: Associations from a multicenter study.

BACKGROUND: Baseline lung allograft dysfunction (BLAD), the failure to achieve ≥80%-predicted spirometry after lung transplant (LTx), is associated with impaired survival. Physiologic abnormalities in BLAD are poorly understood. Airway oscillometry measures respiratory system mechanics and may provide insight into understanding the mechanisms of BLAD. OBJECTIVES: This study aims to describe and measure the association between airway oscillometry parameters [Reactance (Xrs5, Ax), Resistance (Rrs5, Rrs5-19)] (1) stable LTx recipients, comparing those with normal spirometry and those with BLAD; and (2) in recipients with chronic lung allograft dysfunction (CLAD), comparing those with normal baseline spirometry and those with BLAD. METHODS: A multi-center cross-sectional study was performed including bilateral LTx between January 2020 and June 2021. Participants performed concurrent airway oscillometry and spirometry. Multivariable logistic regression was performed to measure the association between oscillometry parameters and BLAD. RESULTS: A total of 404 LTx recipients performed oscillometry and 253 were included for analysis. Stable allograft function was confirmed in 149 (50.2%) recipients (92 (61.7%) achieving normal spirometry and 57 (38.3%) with BLAD). Among stable LTx recipients, lower Xrs5 Z-Score (aOR 0.50 95% CI 0.37-0.76, p = 0.001) was independently associated with BLAD. CLAD was present in 104 (35.0%) recipients. Among recipients with CLAD, lower Xrs5 Z-Score (aOR 0.73 95% CI 0.56-0.95, p = 0.02) was associated with BLAD. CONCLUSIONS: Oscillometry provides novel physiologic insights into mechanisms of BLAD. The independent association between Xrs5 and BLAD, in both stable recipients and those with CLAD suggests that respiratory mechanics, in particular abnormal elastance, is an important physiologic feature. Further longitudinal studies are needed to understand the trajectory of oscillometry parameters in relation to allograft outcomes.

Management of Multidrug Resistant Infections in Lung Transplant Recipients with Cystic Fibrosis.

Cystic fibrosis (CF) is an inherited multisystem disease characterised by bronchiectasis and chronic respiratory infections which eventually cause end stage lung disease. Lung transplantation (LTx) is a well-established treatment option for patients with CF-associated lung disease, improving survival and quality of life. Navigating recurrent infections in the setting of LTx is often difficult, where immune suppression must be balanced against the constant threat of infection. Sepsis/infections are one of the major contributors to post-LTx mortality and multiresistant organisms (eg, Burkholderia cepacia complex, Mycobacterium abscessus complex, Scedosporium spp. and Lomentospora spp.) pose a significant threat to survival. This review will summarize current and novel therapies to assist with the management of multiresistant bacterial, mycobacterial, viral and fungal infections which threaten the CF LTx cohort.

Scedosporium apiospermum and Lomentospora prolificans in lung transplant patients - A single center experience over 24 years.

INTRODUCTION: Scedosporium apiospermum and Lomentospora prolificans (Scedosporium/Lomentospora) species are emerging, multi-resistant pathogens that cause life-threatening illnesses among lung transplant (LTx) recipients. The current epidemiology and management in LTx are unknown. METHODS: We performed a retrospective single center audit of all sputum/bronchoscopy samples for Scedosporium/Lomentospora species in LTx patients over a 24-year period (1995-2019). Patients were diagnosed as colonized or with invasive fungal disease. RESULTS: From a cohort of 962 LTx recipients, 30 patients (3.1%) cultured Scedosporium/Lomentospora (1.2%, 1.9%, respectively). There were no isolates from 1995 to 2013, with multiple yearly isolates thereafter. Nineteen (63%) cases were classified as IFD, and 11 (37%) as colonization. The median time to first culture from transplantation was 929 days (Interquartile-range [IQR] 263-2960). Most patients (63%) had received antifungals prior to the first positive culture of Scedosporium/Lomentospora for other fungal infection. The most common antifungal used for treatment of Scedosporium/Lomentospora was posaconazole (n = 16; 53%). Median duration of therapy was 364 days (IQR 164-616). Treatment was associated with improved lung function over 6 months (median FEV1 increased from 1.3L[IQR 0.9-1.8L] to 1.8L[IQR 1.1-2.3] P = .05). Six patients cultured Scedosporium/Lomentospora prior to transplantation, and no survival disadvantage was seen as compared to our whole LTx cohort (P = .8). CONCLUSION: Our single center 24-year experience suggests that the incidence of Scedosporium/Lomentospora is increasing. Scedosporium/Lomentospora is typically isolated several years after LTx, and requires prolonged anti-fungal treatment that is usually associated with improved in lung function. Culture of Scedosporium/Lomentospora prior to LTx did not pose a survival disadvantage. Further surveillance is required to fully characterize implications of these organisms for LTx recipients.

Outcomes Following Extracorporeal Photopheresis for Chronic Lung Allograft Dysfunction Following Lung Transplantation: A Single-Center Experience.

INTRODUCTION: Survival following lung transplantation (LTx) is limited by the development of chronic lung allograft dysfunction (CLAD), for which there are few effective therapies and no standardized management. Several small studies have demonstrated the effectiveness of extracorporeal photopheresis (ECP) as a therapeutic option for CLAD. METHODS: A retrospective descriptive audit of 12 LTx recipients who received rescue ECP for CLAD over 5 years (2013-2018) at the Alfred Hospital, Melbourne, Australia, was completed. Nonresponders to ECP were defined as patients who experienced a 20% decrease in forced expiratory volume (FEV1) within 6 weeks of commencing therapy. RESULTS: Mean time since LTx was 849 days and mean time since diagnosis of CLAD was 131 days. Fifty-eight percent of patients were male (n = 7) and 67% responded to ECP therapy (n = 8). Among responders, the mean (95% confidence interval) decline in FEV1 pre-ECP was 9.0 mL/day (5-12 mL/day), compared to 1.4 mL/day (0-4 mL/day) post-ECP (P = .01). Among nonresponders, mean (95% confidence interval) decline in FEV1 was 7.2 mL/day (4-10 mL/day) pre-ECP and 5.0 mL/day (3-7 mL/day) post ECP (P = .2). Nonresponders were more likely to be female (P = .01) and neutropenic (P = .005). Patients with prior exposure to anti-thymocyte globulin had a lowered response to ECP. CONCLUSION: Rescue ECP arrested the decline of lung function in 67% of patients with CLAD. Sex, pre-ECP neutrophil count, and exposure to anti-thymocyte globulin may help determine response to ECP. Future clinical trials are needed to confirm this effect, help predict response to therapy, and ultimately guide the placement of ECP in the treatment algorithm for CLAD.

Outcomes following resection of non-small cell lung cancer in octogenarians.

BACKGROUND: The treatment of choice for early stage non-small cell lung cancer (NSCLC) is surgical resection. Little is known about the short- and long-term outcomes among very elderly patients. We sought to determine predictors of short- and long-term survival among octogenarians undergoing curative-intent resection for NSCLC in Victoria, Australia. METHODS: We retrospectively reviewed data from all patients aged ≥80 years who underwent curative-intent resection for NSCLC over 12 years (January 2005-December 2016) across five tertiary centres. We examined effect of age, stage of disease, extent of surgery and lung function on short- and long-term survival. RESULTS: Two hundred patients aged ≥80 years underwent curative-intent resections. Mortality at 30 and 120 days was 2.9% and 5.9%, respectively. Increased early mortality was observed among those ≥83 years, at 30 days (6.8% versus 0.8%, P = 0.044) and 120 days (12.2% versus 2.3%, P = 0.0096). Early mortality was highest among patients ≥83 years requiring lobectomy, compared to sub-lobar resection at 120 days (17% versus 3.8%, P = 0.019). Long-term survival was predicted by age and stage of disease. Among patients with Stage I disease aged <83 years, lobectomy was associated with superior 5-year survival, compared to sub-lobar resection (83% versus 61%, P = 0.02). CONCLUSION: In carefully selected elderly patients undergoing curative-intent resection of early stage NSCLC, both short- and long-term outcomes appear consistent with younger historical cohorts. Early mortality was associated with lobectomy in those with advanced age. Older patients undergoing lobectomy appeared to be at highest risk for early mortality, while younger patients with Stage I disease undergoing at least lobectomy appear to have the best long-term survival.

A complicated cockroach-ectomy.

The exact incidence of foreign body aspiration among adults is unknown, and its clinical presentation is vastly divergent. We report the previously undescribed occurrence of cockroach aspiration in an adult, presenting with a "crawling sensation" in his chest. Flexible endobronchial examination revealed a foreign body impacted in the lingula, resembling the Australian cockroach Periplaneta australasiae. Partial extraction via biopsy forceps was performed and complicated by acute hypoxia on disimpaction, requiring a brief period of bag/mask ventilation. Following the offset of procedural sedation, the remaining foreign body was manually expectorated. A total of 24 h post-procedure, the patient was febrile with positive blood cultures (Micrococcus luteus). We highlight the importance of definitive airway support during endobronchial interventions and raise the question regarding the significance of transient bacteraemia following bronchoscopic manipulation.

Obesity suppresses tumor attributable PSA, affecting risk categorization.

Obesity is linked with more aggressive prostate cancer and higher rates of disease recurrence post treatment. It is unclear if this is due to specific tumor-promoting effects of obesity or diagnostic bias. Patients undergoing prostatectomy were categorized according to their body mass index (BMI). Expected prostate-specific antigen (PSA) levels were calculated for each patient based on tumor characteristics. The effect of obesity on the accuracy of pre-treatment risk categorization was determined, and mediation analysis was used to identify the contribution of biologic vs non-biologic mechanisms to the observed increased risk of biochemical recurrence. Residual tumor-promoting effects were estimated in a survival model controlling for diagnostic error. The following results were obtained. The analysis included 1587 patients. Despite similar rates of adverse pathological features at prostatectomy, biochemical recurrence rates were significantly higher in very obese patients, which persisted after adjustment for stage, grade and PSA. Tumor volume however correlated significantly with BMI (P = 0.004), and the difference in predicted and observed 'tumor-attributable' PSA (Delta-PSA) in very obese patients was greater than three times higher than that of healthy patients (P = 0.0067). Regression analysis indicated that the effect of BMI on tumor volume was fully mediated indirectly by its effect on PSA. Inclusion of this diagnostic error as a covariate in the survival analysis attenuated the effect of BMI on recurrence. In conclusion, being very obese suppresses tumor-associated PSA resulting in a diagnostic bias that is responsible for errors in risk classification, and potentially contributes to a delay in initial presentation.

Mandatory pain scoring at triage reduces time to analgesia.

STUDY OBJECTIVE: We study whether mandatory triage pain scoring and an educational program reduces the time to initial analgesic treatment. METHODS: We performed a prospective interventional study in the emergency department (ED) of an adult tertiary referral hospital and major trauma center. After an observational assessment of baseline time to analgesic administration, we mandated the recording of triage pain scores through our computerized information system. In a second separate phase, we administered a staff educational package on the importance of timely analgesia. We measured time to initial analgesia after each phase and at 12-month follow-up. RESULTS: We studied 35,628 patients (8,743 baseline, 8,462 after mandating pain scoring, 9,043 after the educational program, and 9,380 at follow-up), with 12,925 patients (36.3%) overall receiving analgesics. At baseline, the median time to analgesia was 123 minutes (interquartile range [IQR] 58 to 231 minutes), which reduced with pain scoring (95 minutes; IQR 45 to 194 minutes) but no further with the educational package (98 minutes; IQR 45 to 191 minutes). At 12-month follow-up, the median time to analgesia was 78 minutes (IQR 45 to 143 minutes), 45 minutes (36.4%) faster than at baseline. CONCLUSION: The simple act of altering our ED computerized information system to require pain scoring at triage led to substantially faster provision of initial analgesia, with the effect sustained at 12 months.