Lung transplant airway complications treated with biodegradable airway stents: The Dutch multi-center experience.

INTRODUCTION: Treatment of post lung-transplant airway complications is challenging, and treatment with conventional airway stents is associated with adverse events. More recently, biodegradable airway stents (BDS) have been introduced and may be used to reduce these adverse events. In this study we explore the feasibility of treatment with BDS post lung transplant. METHODS: All patients treated with BDS in The Netherlands were included in this retrospective multicenter study. Feasibility, life span of the stent, occurrence of adverse events, and evolution of lung function were evaluated. RESULTS: Twelve patients (six malacia and six stenosis) received a total of 57 BDS, ranging from 1 to 10 BDS per patient. Six patients had been pretreated with conventional airway stents. Median stent life span was 112 days (range 66-202). No adverse events occurred during stent placement. In 5 out of 57 stent placements, a single additional bronchoscopy was necessary because of mucus accumulation (n = 4) or excessive granulation tissue (n = 1). All stent naïve patients became airway stent independent after treatment; all patients pretreated with conventional airway stents were still airway stent dependent at the end of follow up. CONCLUSION: Treatment with BDS is safe and feasible. Adverse events were mild and easily treatable. All patients with initial treatment with BDS were airway stent independent at the end of follow up with a median treatment of 4 BDS.

Clinical Characteristics and Outcomes of Immunocompromised Patients With Coronavirus Disease 2019 Caused by the Omicron Variant: A Prospective, Observational Study.

BACKGROUND: Illness after infection with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron variant is less severe compared with previous variants. Data on the disease burden in immunocompromised patients are lacking. We investigated the clinical characteristics and outcomes of immunocompromised patients with coronavirus disease 2019 (COVID-19) caused by Omicron. METHODS: Organ transplant recipients, patients on anti-CD20 therapy, and allogenic hematopoietic stem cell transplantation recipients infected with the Omicron variant were included. Characteristics of consenting patients were collected and patients were contacted regularly until symptom resolution. To identify possible risk factors for hospitalization, a univariate logistic analysis was performed. RESULTS: 114 consecutive immunocompromised patients were enrolled. Eighty-nine percent had previously received 3 mRNA vaccinations. While only 1 patient died, 23 (20%) were hospitalized for a median of 11 days. A low SARS-CoV-2 immunoglobulin G (IgG) antibody response (<300 BAU [binding antibody units]/mL) at diagnosis, being older, being a lung transplant recipient, having more comorbidities, and having a higher frailty score were associated with hospital admission (all P < .01). At the end of follow-up, 25% had still not fully recovered. Of the 23 hospitalized patients, 70% had a negative and 92% had a low IgG (<300 BAU/mL) antibody response at admission. Sotrovimab was administered to 17 of these patients, and 1 died. CONCLUSIONS: While the mortality in immunocompromised patients infected with Omicron was low, hospital admission was frequent and the duration of symptoms often prolonged. In addition to vaccination, other interventions are needed to limit the morbidity from COVID-19 in immunocompromised patients.

Developments in lung transplantation over the past decade.

With an improved median survival of 6.2 years, lung transplantation has become an increasingly acceptable treatment option for end-stage lung disease. Besides survival benefit, improvement of quality of life is achieved in the vast majority of patients. Many developments have taken place in the field of lung transplantation over the past decade. Broadened indication criteria and bridging techniques for patients awaiting lung transplantation have led to increased waiting lists and changes in allocation schemes worldwide. Moreover, the use of previously unacceptable donor lungs for lung transplantation has increased, with donations from donors after cardiac death, donors with increasing age and donors with positive smoking status extending the donor pool substantially. Use of ex vivo lung perfusion further increased the number of lungs suitable for lung transplantation. Nonetheless, the use of these previously unacceptable lungs did not have detrimental effects on survival and long-term graft outcomes, and has decreased waiting list mortality. To further improve long-term outcomes, strategies have been proposed to modify chronic lung allograft dysfunction progression and minimise toxic immunosuppressive effects. This review summarises the developments in clinical lung transplantation over the past decade.

Desquamative interstitial pneumonia: a systematic review of its features and outcomes.

BACKGROUND: Desquamative Interstitial Pneumonia (DIP) is a rare form of idiopathic interstitial pneumonia (IIP). Data on clinical features, aetiology, prognosis and effect of treatment strategies are limited. We aimed to collect all published cases to better characterise DIP. METHODS: A systematic literature search was performed for all original cases of adult patients with histopathologically-confirmed DIP. Individual patient data were extracted and summarised. RESULTS: We included 68 individual cases and 13 case series reporting on 294 cases. Most common presenting symptoms were dyspnoea and cough. Pulmonary function showed a restrictive pattern (71%) with decreased diffusion capacity. We found a high incidence (81%) of ever smoking in patients with DIP and 22% of patients had other (occupational) exposures. Characteristic features on high-resolution computed tomography (HRCT) scan were bilateral ground-glass opacities with lower lobe predominance (92%). Treatment and duration of treatment widely varied. Initial response to treatment was generally good, but definitely not uniformly so. A significant proportion of patients died (25% of individual cases) or experienced a relapse (18% of individual cases). CONCLUSION: DIP remains an uncommon disease, frequently but not always related to smoking or other exposures. Furthermore, DIP behaves as a progressive disease more often than generally thought, possibly associated with different underlying aetiology.

Assessment of Cotinine Reveals a Dose-Dependent Effect of Smoking Exposure on Long-term Outcomes After Renal Transplantation.

BACKGROUND: Smoking is a risk factor for poor late outcomes in renal transplant recipients (RTR). Smoking exposure can be assessed by self-report and cotinine measurements. We investigated whether use of cotinine as a biomarker for smoking exposure can serve as an alternative for self-report and to compare associations of smoking exposure by self-report and cotinine with outcomes in RTR and assess dose dependency. METHODS: Renal transplant recipients were classified as never, former, light (≤10 cigarettes/day), and heavy smokers (>10 cigarettes/day) according to self-report and analogous categories for urine and plasma cotinine. First, we assessed agreement of self-reported smoking exposure with smoking exposure according urine and plasma cotinine. Second, we compared the associations with graft failure and mortality. RESULTS: Of 603 RTR (age 51.5 ± 12.1 years, 55% men), 36.0% RTR were never, 42.3% former, 10.6% light, and 11.1% heavy smokers according to self-report. The majority (98.6%) of never smokers had nondetectable cotinine. However, 14 and 13 RTR reporting no active smoking had respective urine or plasma cotinine consistent with active smoking. Cotinine-based measurements were dose-dependently associated with mortality and graft failure. CONCLUSIONS: Plasma and urine cotinine can serve as an alternative to self-report and were dose-dependently associated with poor late outcomes in RTR.

Adalimumab for Crohn's disease: long-term sustained benefit in a population-based cohort of 438 patients.

BACKGROUND AND AIMS: Adalimumab is an effective therapy for induction and maintenance of Crohn's disease. However, results in clinical trials don't necessarily reflect daily clinical practice. Therefore, we assessed real-life long-term clinical response to adalimumab in a large population-based cohort and identified clinical parameters affecting response METHODS: All consecutive patients in North-Holland that started adalimumab between 2003 and 2011 were included, of which medical charts were reviewed. Response to induction therapy was assessed after 3months. Sustained benefit of maintenance therapy was calculated from Kaplan-Meier survival tables depicting ongoing adalimumab treatment. Regression analyses were performed to identify factors predicting response to adalimumab therapy. RESULTS: In total 438 Crohn's patients started adalimumab with 92.5% response to the induction phase. After 1year 83.3% showed sustained benefit of maintenance treatment, followed by 74.0% after 2years. Nevertheless, one third of patients were in steroid-free remission at the end of their follow-up. Response to induction was negatively affected by longer disease duration (OR 1.05; p<0.01) and strictures (OR 3.73; p=0.04). Increased CRP levels predicted higher rates of initial response (OR 0.31; p<0.01). Concomitant thiopurines in the first 6months of adalimumab treatment decreased the risk to fail maintenance therapy (HR 0.69, p=0.05). Previous infliximab therapy did not affect response to adalimumab, however dose escalation was more often deemed necessary (p<0.01). CONCLUSION: Adalimumab was successful in the majority of patients, with 10% loss of response per subsequent year. Concomitant thiopurines might improve adalimumab maintenance treatment.

Is albuminuria screening and treatment optimal in patients with type 2 diabetes in primary care? Observational data of the GIANTT cohort.

BACKGROUND: Failure of diagnosing and treatment of albuminuria play a role in morbidity and mortality in type 2 diabetes (T2DM). We evaluated guideline adherence and factors associated with albuminuria screening and treatment in T2DM patients in primary care. METHODS: Guidelines recommend annual measurement of albuminuria and, if increased, treatment with renin-angiotensin-aldosterone system (RAAS) blockers. We performed a cohort study of T2DM patients managed by 182 Dutch general practitioners (GPs; Groningen Initiative to Analyse Type 2 diabetes Treatment database), and evaluated guideline adherence in the years 2007-2009. We assessed whether demographic, clinical, organizational or provider factors determined guideline adherence with multilevel analyses. RESULTS: Data were available for 14 120 T2DM patients [47.6% male, mean age 67.3 ± 11.7 years, median diabetes duration 6 (IQR: 3-10) years]. The albumin-creatinine ratio (ACR) was measured in 45.2% in 2007, 57.4% in 2008 and 56.8% in 2009. Only 23.7% of all patients were measured every year and 21.4% were never measured. The ACR was more often measured in patients <75 years, with a previous ACR measurement, using anti-diabetic medication, and receiving additional care by a diabetes support facility. RAAS treatment was prescribed to 78.4% of patients with prevalent micro/macroalbuminuria, 66.5% with incident micro/macroalbuminuria, 59.3% with normoalbuminuria and 52.1% of those without ACR measurements. In those not treated with RAAS blockers, it was initiated in 14.3, 12.3, 3.0 and 2.3%, respectively. The presence of micro/macroalbuminuria, higher blood pressure, incidence of cardiovascular events and treatment with antihypertensive medication were the determinants of RAAS-treatment initiation. CONCLUSIONS: Guideline implementation regarding the management of albuminuria in T2DM patients in primary care should be further improved.

Incidence of impaired renal function after lung transplantation.

BACKGROUND: Impaired renal function is a frequent complication after lung transplantation (LTx). Since the early days of LTx, recipient eligibility criteria slowly became less strict, while treatment regimens evolved. These developments may have had opposing effects on the risk for impaired renal function. We aimed to study changes in recipient characteristics in conjunction with incidence of impaired renal function in consecutive series of lung transplant recipients (LTRs). METHODS: Three hundred forty adult LTRs (mean age 45 ± 12 years, 50.3% male, median follow-up 3.4 [1.0 to 7.1] years) were divided into four consecutive patient time-series: 1990 to 1996 (n = 93); 1997 to 2001 (n = 79); 2002 to 2005 (n = 89); and 2006 to 2008 (n = 79). The primary end-point was cumulative incidence of doubling of serum creatinine (DSC), taking into account the competing risk of death. Measured glomerular filtration rate (mGFR; (125)I-Iothalamate) was assessed as a secondary end-point. RESULTS: Mean age at transplantation (p = 0.001), prevalence of hypertension (p = 0.005), pack-years of former smoking (p = 0.001) and body mass index (p = 0.05) increased across the consecutive series. The cumulative incidence of DSC at 24 months after LTx was 43%, 37%, 35% and 29%, respectively, in the consecutive series (p = 0.01). Despite higher prevalence of renal risk factors, there was lower adjusted risk of DSC in the consecutive series, with hazard ratios [95% CI] of 0.62 [0.34 to 1.15], 0.50 [0.25 to 0.98] and 0.31 [0.154 to 0.67], respectively, compared with the 1990 to 1996 series. Accordingly, mGFRs at 24 months after LTx were 51 ± 17, 53 ± 17, 57 ± 21 and 63 ± 21 ml/min/1.73 m(2) in the consecutive series (p = 0.002). CONCLUSIONS: Despite the higher prevalence of renal risk factors in more recently transplanted patients, renal outcome after LTx has improved over time. Nevertheless, impaired renal function remains a frequent complication after LTx.

Smoking is a risk factor for graft failure and mortality after renal transplantation.

BACKGROUND: Smoking in renal transplant recipients (RTR) is an acknowledged cardiovascular risk factor. It is, however, unclear whether smoking also increases the risk of graft failure (GF). METHOD: In this study, we prospectively assessed the association of current smoking versus past and never smoking with GF and mortality in 604 RTR (age 51.5 ± 12.1 years, 55% male). RESULTS: At inclusion, 133 (22%) were current smokers, 255 (42%) were past smokers and 216 (36%) never smoked. During follow-up of 5.3 (4.7-5.7) years, 41 (7%) RTR experienced GF and 95 RTR (16%) died. Current smoking RTR had higher risk for GF compared to never smoking RTR (hazard ratio, HR = 3.3, 95% CI 1.5-7.1, p = 0.002). Past smoking RTR had similar risk of GF as never smoking RTR (HR = 1.1, 95% CI 0.5-2.6, p = 0.7). Current smoking RTR and past smoking RTR were at higher risk for death than never smoking RTR (HR = 2.1, 95% CI 1.1-3.8, p = 0.016, and HR = 2.4, 95% CI 1.4-4.0, p = 0.001, respectively). CONCLUSION: Smoking after renal transplantation is associated with risk for GF and mortality. Since past smoking is a risk factor for mortality but not for GF, smoking cessation may be beneficial to RTR in delaying GF in long term.