Explore the vast range of titles available.

Combined pulmonary fibrosis and emphysema (CPFE) is an underrecognized syndrome characterized by chronic, progressive disease with a dismal prognosis. Frequent co-morbidities with a higher incidence than in idiopathic pulmonary fibrosis or emphysema alone are pulmonary hypertension (WHO group 3) in 47-90% of the patients and lung cancer in 46.8% of the patients. Review current evidence and knowledge concerning diagnosis, risk factors, disease evolution and treatment options of CPFE. We searched studies reporting CPFE in original papers, observational studies, case reports, and meta-analyses published between 1990 and August 2020, in the PubMed, Embase, Cochrane Library, Wiley Online Library databases and Google Scholar using the search terms [CPFE], [pulmonary fibrosis] OR [IPF] AND [emphysema]. Bibliographies of retrieved articles were searched as well. Further inclusion criteria were publications in English, French, German and Italian, with reference to humans. In vitro data and animal data were not considered unless they were mentioned in studies reporting predominantly human data. Between May 1, 1990, and September 1, 2020, we found 16 studies on CPFE from the online sources and bibliographies. A total of 890 patients are described in the literature. Although male/female ratio was not reported in all studies, the large majority of patients were male (at least 78%), most of them were current or former heavy smokers. CPFE is a syndrome presenting with dyspnea on exertion followed by disruptive cough and recurrent exacerbations. The disease may progress rapidly, be aggravated by pulmonary hypertension WHO group 3 and is associated with an increased risk of lung cancer. Smoking and male sex are important risk factors. There is a need for more research on CPFE especially relating to etiology, influence of genetics, treatment and prevention options. Antifibrotic therapy might be an interesting treatment option for these patients.

Pharmacotherapy after lung transplantation is complex and prone to drug-drug interactions, dosing errors, and toxicity. We retrospectively analysed 259 comments from weekly interdisciplinary rounds at the University Hospital Zurich between September 2022 and April 2024 to identify common pharmacological pitfalls in inpatient lung transplant recipients. The cohort included 62 patients (mean age 56.1 years; 40.3% female). Most comments concerned potential risks rather than confirmed harm: 54.4% were classified as potential side effects and 21.6% as potential loss of effectiveness. Interactions were the most frequent subcategory (45.6%), followed by dosage problems (14.3%). Tacrolimus was the most commonly commented on drug, often due to interactions with metamizole/dipyrone, resulting in fluctuating tacrolimus levels. Other frequent issues included QTc-prolonging combinations (e.g., domperidone with escitalopram or amiodarone in addition to itraconazole) and reduced levothyroxine absorption due to divalent cations. Only five comments reflected actual adverse outcomes, indicating overall high drug safety. These findings are consistent with the literature describing the importance of systematic pharmacological review and interdisciplinary collaboration to improve medication safety and standardise care in lung transplant recipients.

Since candidates with comorbidities are increasingly referred for lung transplantation, knowledge about comorbidities and their cumulative effect on outcomes is scarce. We retrospectively collected pretransplant comorbidities of all 513 adult recipients transplanted at our center between 1992–2019. Multiple logistic- and Cox regression models, adjusted for donor-, pre- and peri-operative variables, were used to detect independent risk factors for primary graft dysfunction grade-3 at 72 h (PGD3-T72), onset of chronic allograft dysfunction grade-3 (CLAD-3) and survival. An increasing comorbidity burden measured by Charleston-Deyo-Index was a multivariable risk for survival and PGD3-T72, but not for CLAD-3. Among comorbidities, congestive right heart failure or a mean pulmonary artery pressure >25 mmHg were independent risk factors for PGD3-T72 and survival, and a borderline risk for CLAD-3. Left heart failure, chronic atrial fibrillation, arterial hypertension, moderate liver disease, peptic ulcer disease, gastroesophageal reflux, diabetes with end organ damage, moderate to severe renal disease, osteoporosis, and diverticulosis were also independent risk factors for survival. For PGD3-T72, a BMI>30 kg/m2 was an additional independent risk. Epilepsy and a smoking history of the recipient of >20packyears are additional independent risk factors for CLAD-3. The comorbidity profile should therefore be closely considered for further clinical decision making in candidate selection.

Lung transplant patients are a vulnerable group of immunosuppressed patients that are prone to frequent respiratory infections. We studied 60 episodes of respiratory symptoms in 71 lung transplant patients. Almost half of these episodes were of unknown infectious etiology despite extensive routine diagnostic testing. We re-analyzed respiratory samples of all episodes with undetermined etiology in order to detect potential viral pathogens missed/not accounted for in routine diagnostics. Respiratory samples were enriched for viruses by filtration and nuclease digestion, whole nucleic acids extracted and randomly amplified before high throughput metagenomic virus sequencing. Viruses were identified by a bioinformatic pipeline and confirmed and quantified using specific real-time PCR. In completion of routine diagnostics, we identified and confirmed a viral etiology of infection by our metagenomic approach in four patients (three Rhinovirus A, one Rhinovirus B infection) despite initial negative results in specific multiplex PCR. Notably, the majority of samples were also positive for Torque teno virus (TTV) and Human Herpesvirus 7 (HHV-7). While TTV viral loads increased with immunosuppression in both throat swabs and blood samples, HHV-7 remained at low levels throughout the observation period and was restricted to the respiratory tract. This study highlights the potential of metagenomic sequencing for virus diagnostics in cases with previously unknown etiology of infection and in complex diagnostic situations such as in immunocompromised hosts.

T-cell response plays an important role in SARS-CoV-2 immunogenicity. For people living with HIV (PWH) and solid organ transplant (SOT) recipients there is limited evidence on the reliability of commercially available T-cell tests. We assessed 173 blood samples from 81 participants (62 samples from 35 PWH; 111 samples from 46 SOT recipients [lung and kidney]) with two commercial SARS-CoV-2 Interferon-γ (IFN-γ) release assays (IGRA; SARS-CoV-2 IGRA by Euroimmun, and IGRA SARS-CoV-2 by Roche). The reliability between the tests was judged as low (Cohen’s kappa [κ] = 0.20; overall percent agreement [OPA] = 66%). A high proportion of tests were invalid (22% Euroimmun; 8% Roche). When excluding these invalid tests, the agreement was higher (κ  =  0.43; OPA = 90%). The low reliability between the two T-cell tests indicates that results should be interpreted with caution in SOT recipients and PWH and that SARS-CoV-2 T-cell tests need to be optimized and further validated for use in vulnerable patient populations.

Diagnosis of acute lung allograft rejection is currently based on transbronchial lung biopsies. Additional methods to detect acute allograft dysfunction derived from plasma and bronchoalveolar lavage samples might facilitate diagnosis and ultimately improve allograft survival. This review article gives an overview of the cell profiles of bronchoalveolar lavage and plasma samples during acute lung allograft rejection. The value of these cells and changes within the pattern of differential cytology to support the diagnosis of acute lung allograft rejection is discussed. Current findings on the topic are highlighted and trends for future research are identified.

After hospitalization due to acute COPD exacerbations, patient-manageable behaviors influence rehospitalization frequency. This study's aim was to develop a hospital-ward-initiated Behaviour-Change-Wheel (BCW)-based intervention targeting patients' key health behaviors, with the aim to increase quality of life and reduce rehospitalization frequency. Intervention development was performed by University Hospital Zurich working groups and followed the three BCW stages for each of the three key literature-identified problems: insufficient exacerbation management, lack of physical activity and ongoing smoking. In stage one, by analyzing published evidence including but not limited to patients' perspective--and health professionals' perspectives regarding these problems, we identified six target behaviors. In stage two, we identified six corresponding intervention functions. As our policy category, we chose developing guidelines and service provision. For stage three, we defined eighteen basic intervention packages using 46 Behaviour Change Techniques in our basic intervention. The delivery modes will be face-to-face and telephone contact. In the inpatient setting, this behavioral intervention will be delivered by a multi-professional team. For at least 3 months following discharge, an advanced nursing practice team will continue and coordinate the necessary care package via telephone. The intervention is embedded in a broader self-management intervention complemented by integrated care components. The BCW is a promising foundation upon which to develop our COPD intervention. In future, the interaction between the therapeutic care team-patient relationships and the delivery of the behavioral intervention will also be evaluated. Keywords: AECOPD, complex intervention, behavior, behavior change, intervention development

Achieving adequate immunosuppression for lung transplant recipients in the first year after lung transplantation is a key challenge. Prophylaxis of allograft rejection must be balanced with the adverse events associated with immunosuppressive drugs, for example infection, renal failure, and diabetes. A triple immunosuppressive combination is standard, including a steroid, a calcineurin inhibitor, and an antiproliferative compound beginning with the highest levels of immunosuppression and a subsequent tapering of the dose, usually guided by therapeutic drug monitoring and considering clinical results, bronchoscopy sampling results, and additional biomarkers such as serum viral replication or donor-specific antibodies. Balancing the net immunosuppression level required to prevent rejection without overly increasing the risk of infection and other complications during the tapering phase is not well standardized and requires repeated assessments for dose-adjustments. In our adaptive immunosuppression approach, we additionally consider results from the white blood cell counts, in particular lymphocytes and eosinophils, as biomarkers for monitoring the level of immunosuppression and additionally use them as therapeutic targets to fine-tune the immunosuppressive strategy over time. The concept and its rationale are outlined, and areas of future research mentioned.

The role of differential cytology patterns in peripheral blood and bronchoalveolar lavage samples is increasingly investigated as a potential adjunct to diagnose acute and chronic allograft dysfunction after lung transplantation. While these profiles might facilitate the diagnosis of acute cellular rejection, low sensitivity and specificity of these patterns limit direct translation in a clinical setting. In this context, the identification of other biomarkers is needed. This review article gives an overview of cytokine profiles of plasma and bronchoalveolar lavage samples during acute cellular rejection. The value of these cytokines in supporting the diagnosis of acute cellular rejection is discussed. Current findings on the topic are highlighted and experimental settings for future research projects are identified.

Abstract We conducted a single-center, randomized, placebo-controlled trial to determine whether streptokinase instillations adjunctive to chest tube drainage reduce the need for surgery and improve outcome in patients with pleural empyema. Fifty-three patients (frank pus aspirated, 81%; microbiological agent cultured, 62%; mean effusion pH, 6.6 ± 0.4) received antibiotic treatment, chest tube drainage, and once-daily pleural rinses with either normal saline or normal saline with streptokinase (250,000 IU). Nine patients were excluded for various reasons before pleural rinses were started. Streptokinase (n = 22) was instilled over 4.5 ± 2 days and saline (n = 22) was instilled over 3 ± 1.3 days. One patient in each group died during treatment. Clinical treatment success and need for referral to surgery were the main outcome measures. No difference was observed after 3 days. After 7 days, streptokinase-treated patients had a higher clinical success rate (82 vs. 48%, p = 0.01) and fewer referrals for surgery (45 vs. 9%, p = 0.02). No significant radiologic or functional differences were observed between groups during follow-up over 6 months. We conclude that intrapleural streptokinase adjunctive to chest tube drainage reduces the need for surgery and improves the clinical treatment success in patients with pleural empyema.