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  • Lu LY
  • Lee HM
  • Burke A
  • Li Bassi G
  • Torres A
  • et al.
Chest. 2024 Mar;165(3):540-558 doi: 10.1016/j.chest.2023.09.019.
BACKGROUND:

Influenza-associated pulmonary aspergillosis (IAPA) increasingly is being reported in critically ill patients. We conducted this systematic review and meta-analysis to examine the prevalence, risk factors, clinical features, and outcomes of IAPA.

STUDY QUESTION:

What are the prevalence, risk factors, clinical features, and outcomes of IAPA in critically ill patients?

STUDY DESIGN AND METHODS:

Studies reporting IAPA were searched in the following databases: PubMed MEDLINE, CINAHL, Cochrane Library, Embase, Scopus, Cochrane Trials, and ClinicalTrials.gov. We performed one-group meta-analysis on risk factors, clinical features, morbidity, and mortality using random effects models.

RESULTS:

We included 10 observational studies with 1,720 critically ill patients with influenza, resulting in an IAPA prevalence of 19.2% (331 of 1,720). Patients who had undergone organ transplantation (OR, 4.8; 95% CI, 1.7-13.8; I2 = 45%), harbored a hematogenous malignancy (OR, 2.5; 95% CI, 1.5-4.1; I2 = 0%), were immunocompromised (OR, 2.2; 95% CI, 1.6-3.1; I2 = 0%), and underwent prolonged corticosteroid use before admission (OR, 2.4; 95% CI, 1.4-4.3; I2 = 51%) were found to be at a higher risk of IAPA developing. Commonly reported clinical and imaging features were not particularly associated with IAPA. However, IAPA was associated with more severe disease progression, a higher complication rate, and longer ICU stays and required more organ supports. Overall, IAPA was associated with a significantly elevated ICU mortality rate (OR, 2.6; 95% CI, 1.8-3.8; I2 = 0%).

INTERPRETATION:

IAPA is a common complication of severe influenza and is associated with increased mortality. Early diagnosis of IAPA and initiation of antifungal treatment are essential, and future research should focus on developing a clinical algorithm.

TRIAL REGISTRY:

International Prospective Register of Systematic Reviews; No.: CRD42022284536; URL: https://www.crd.york.ac.uk/prospero/.

  • Acuña-Chávez LM
  • Cruzalegui-Bazán C
  • Quispe-Vicuña C
  • Saldarriaga C
  • Contreras J
  • et al.
Monaldi Arch Chest Dis. 2022 Sep 5;93(2) doi: 10.4081/monaldi.2022.2402.

Red blood cell distribution width (RDW) has been shown to have prognostic value in a number of different clinical settings, such as cardiovascular disease, including heart failure. However, its prognostic value in heart transplant (HT) recipients remains unknown. The aim of this systematic review is to determine the prognostic value of pre-transplant RDW for mortality in HT recipients. There is a pre-published protocol of this review. The terms "Heart transplant", "Red cell distribution width" and their synonyms were used in the search strategy. PubMed/Medline, Embase, Scopus, Web of Science and LILACS were searched until May 17th, 2022, without date or language restrictions. Two authors independently carried out the selection, first by title and abstract, second by full-text revision. Discrepancies were discussed and resolved with three other authors. Quality of individual studies was assessed with Newcastle Ottawa Scale (NOS) for cohorts. After removing the duplicates, 3885 articles were identified. Four articles were included in the qualitative synthesis. Three studies were classified as "good quality": whereas one as "poor quality" according to NOS scale. All the included articles evaluated long-term mortality and one study also evaluated short-term mortality. In this one, a correlation between higher RDW values and short-term mortality was reported. Meanwhile, in all the studies, a high pre-HT RDW was a marker of long-term mortality following cardiac transplantation. Our review shows that an elevated on-admission RDW is associated with long-term mortality in heart transplantation recipients.

  • Rahaghi FF
  • Kolaitis NA
  • Adegunsoye A
  • de Andrade JA
  • Flaherty KR
  • et al.
Chest. 2022 Jul;162(1):145-155 doi: 10.1016/j.chest.2022.02.012.
BACKGROUND:

Pulmonary hypertension (PH) is a common complication of interstitial lung disease (ILD) and is associated with worse outcomes and increased mortality. Evaluation of PH is recommended in lung transplant candidates, but there are currently no standardized screening approaches. Trials have identified therapies that are effective in this setting, providing another rationale to routinely screen patients with ILD for PH.

RESEARCH QUESTION:

What screening strategies for identifying PH in patients with ILD are supported by expert consensus?

STUDY DESIGN AND METHODS:

The study convened a panel of 16 pulmonologists with expertise in PH and ILD, and used a modified Delphi consensus process with three surveys to identify PH screening strategies. Survey 1 consisted primarily of open-ended questions. Surveys 2 and 3 were developed from responses to survey 1 and contained statements about PH screening that panelists rated from -5 (strongly disagree) to 5 (strongly agree).

RESULTS:

Panelists reached consensus on several triggers for suspicion of PH including the following: symptoms, clinical signs, findings on chest CT scan or other imaging, abnormalities in pulse oximetry, elevations in brain natriuretic peptide (BNP) or N-terminal pro-brain natriuretic peptide (NT-proBNP), and unexplained worsening in pulmonary function tests or 6-min walk distance. Echocardiography and BNP/NT-proBNP were identified as screening tools for PH. Right heart catheterization was deemed essential for confirming PH.

INTERPRETATION:

Many patients with ILD may benefit from early evaluation of PH now that an approved therapy is available. Protocols to evaluate patients with ILD often overlap with evaluations for pulmonary hypertension-interstitial lung disease and can be used to assess the risk of PH. Because standardized approaches are lacking, this consensus statement is intended to aid physicians in the identification of patients with ILD and possible PH, and provide guidance for timely right heart catheterization.

  • Yaqoob H
  • Jain A
  • Epelbaum O
Chest. 2020;158(4):A771-A771 doi: 10.1016/j.chest.2020.08.718.
CHEST Annual Meeting October 18-21, 2020
  • Boparai S
  • Thurlapati A
  • Hansra R
Chest. 2020;158(4):A2387-A2387 doi: 10.1016/j.chest.2020.08.2026.
CHEST Annual Meeting October 18-21, 2020
  • Modugula S
  • Adroja S
  • Lim JM
  • Daoud A
  • Harris R
Chest. 2020;158(4):A534-A535 doi: 10.1016/j.chest.2020.08.506.
CHEST Annual Meeting October 18-21, 2020
  • Omar A
  • Patil PD
  • Hoshi S
  • Huang J
  • Collum E
  • et al.
Chest. 2018 Jun;153(6):e153-e157 doi: 10.1016/j.chest.2017.10.034.

A 68-year-old man presented to our ED with shortness of breath, weakness, and a 25-lb unintentional weight loss. He had undergone bilateral lung transplantation (cytomegalovirus [CMV]: donor+, recipient+; Epstein-Barr virus: donor+; recipient+) for idiopathic pulmonary fibrosis (IPF) 18 months prior. His posttransplant course was fairly unremarkable until 1 month earlier, when he was admitted for breathlessness and weakness. CT of the chest during that admission revealed mild intralobular and interlobular septal thickening. A bronchoscopy with BAL and transbronchial biopsies did not show acute cellular rejection, but the BAL fluid was positive for coronavirus. His cortisol level was undetectable; he was diagnosed with adrenal insufficiency and fludrocortisone was initiated. He was taking prednisone, tacrolimus, and everolimus for immunosuppression and valganciclovir, itraconazole, and trimethoprim-sulfamethoxazole for antimicrobial prophylaxis. His 25-lb weight loss occurred over the span of just one month.

  • Bhorade SM
  • Husain AN
  • Liao C
  • Li LC
  • Ahya VN
  • et al.
Chest. 2013 Jun;143(6):1717-1724 doi: 10.1378/chest.12-2107.
CET Conclusion
Reviewer: Centre for Evidence in Transplantation
Conclusion: This is an interesting report looking at 481 transbronchial biopsy specimens that were graded by the local pathologist and central pathologist. Using the International Society of Heart and Lung Transplantation grading for acute rejection there was an overall concurrence rate of 74% and 89% respectively for grade A and grade B biopsies respectively. The biopsy specimens were from the AIRSAC trial and the results show that there is considerable interobserver variability in grading of transbronchial biopsy specimens after lung transplantation.
Aims: To determine the interobserver variability in grading transbronchial biopsy specimens for acute rejection after lung transplantation as part of the AIRSAC (Comparison of a Tacrolius/Sirolimus/Prednisone Regimen vs Tacrolimus/Azathioprine/Prednisone Immunosuppressive Regimen in lung transplantation) study.
Interventions: All patients received IL-2 receptor antagonist induction therapy followed by initial immunosuppression with tacrolimus, azathioprine and corticosteroids until 90 days post transplant. The randomized groups were then administered with either tacrolimus, azathioprine and prednisone or tacrolimus, sirolimus and prednisone.
Participants: 181 adult lung transplant recipients aged between 18-65 years.
Outcomes: The outcomes included transbronchial biopsy specimen grading between each site pathologist and the central pathologist. The grading of the specimens were also collected during specific time points after transplantation to determine if time after transplant had an impact on variability on the biopsy specimen interpretation.
Follow Up: 3 years following lung transplantation.
BACKGROUND:

Acute rejection remains a major source of morbidity after lung transplantation. Given the importance of this diagnosis, an international grading system was developed to standardize the diagnosis of acute lung-allograft rejection. The reliability of this grading system has not been adequately assessed by previous studies.

METHODS:

We examined the level of agreement in grading transbronchial biopsy specimens obtained from a large multicenter study (AIRSAC [Comparison of a Tacrolimus/Sirolimus/Prednisone Regimen vs Tacrolimus/Azathioprine/Prednisone Immunosuppressive Regimen in Lung Transplantation] trial). Biopsy specimens were initially graded for acute rejection and lymphocytic bronchiolitis by the site pathologist and subsequently graded by a central pathologist. Reliability of interobserver grading was evaluated using Cohen κ coefficients.

RESULTS:

A total of 481 transbronchial biopsy specimens were graded by both the site and central pathologists. The overall concordance rates were 74% and 89% for grade A and grade B biopsy specimens, respectively. When samples from biopsies performed at different time points after transplantation were assessed, there was a higher level of agreement early (≤ 6 weeks) after transplant compared with later time points for acute rejection. However, there was still only moderate agreement for both grade A (κ score 0.479; 95% CI, 0.29-0.67) and grade B (κ score 0.465; 95% CI, 0.08-0.85) rejection.

CONCLUSIONS:

These results expand upon previous reports of interobserver variability in grading transbronchial biopsy specimens after lung transplantation. Given the variability in grading these specimens, we advocate further education of the histopathologic findings in lung transplant biopsy specimens, as well as revisiting the current criteria for grading transbronchial biopsy specimens to improve concordance among lung transplant pathologists.

TRIAL REGISTRY:

ClinicalTrials.gov; No. NCT00321906; URL: www.clinicaltrials.gov.

  • Finlen Copeland CA
  • Vock DM
  • Pieper K
  • Mark DB
  • Palmer SM
  • et al.
Chest. 2013 Mar;143(3):744-750 doi: 10.1378/chest.12-0971.
CET Conclusion
Reviewer: Mr Simon Knight, Centre for Evidence in Transplantation, The Royal College of Surgeons of England.
Conclusion: This manuscript reports a longitudinal analysis of quality of life (QOL; as measured by the non-disease-specific SF-36 questionnaire) in lung transplant recipients enrolled in a clinical trial of CMV prophylaxis. As such, it is not comparative, but merely follows up all patients enrolled into the trial and assesses quality of life at baseline, 3, 6, 9 and 12 months post-transplant. The authors find that whilst there is a significant increase in physical quality of life over the 12-month period, psychological well-being does not improve and remains significantly below that expected in a normal population. This suggests that more attention needs to be paid in future research to factors that affect the psychological well-being of transplant recipients. Of note, the analysis includes all patients in the study who completed at least one post-transplant QOL assessment. The authors recognise that not all patients completed assessments at all time-points, but there is no information in the manuscript as to exactly how much data were missing.
Aims: To investigate whether lung transplantation confers a one year quality of life (QOL) benefit for physiological and psychological wellbeing and to determine whether the benefits vary by sex, native disease, age, or type of organ transplant operation.
Interventions: QOL was assessed by the Medical Outcomes Study 36-item Short Form Health Survey, version 2. Patients completed the survey prior to and at 3,6,9 and 12 months after lung transplantation.
Participants: 131 adult first lung recipients that participated in the multicenter, prospective, randomized, placebo controlled cytomegalovirus prevention trial from 2003-2007.
Outcomes: The QOL was analysed using the physical health summary and mental health summary at baseline and serially over the first post transplant year. Separate models assessed the association of sex, indication for transplant, age or transplant type on baseline and post-transplant QOL.
Follow Up: 12 months.
BACKGROUND:

Quality of life (QOL) is an important but understudied outcome after lung transplantation. Previous cross-sectional, single-center studies suggest improved QOL, but few prior longitudinal multicenter data exist regarding the effect of transplantation on the patient’s QOL.

METHODS:

We hypothesized that lung transplantation confers a 1-year QOL benefit in both physical and psychologic well-being; we further hypothesized that the magnitude of benefit would vary by sex, native disease, age, or type of transplant operation. To test these hypotheses, we conducted a secondary analysis using QOL data prospectively and serially measured with the Medical Outcomes Study 36-Item Short-Form Health Survey, version 2 (SF-36) in a multicenter cytomegalovirus prevention clinical trial. Linear mixed-effects models were used to assess the impact of transplantation on the recipient’s QOL.

RESULTS:

Over the first year after lung transplantation, the SF-36 Physical Component Score significantly increased an average of 10.9 points from baseline levels (P < .0001). A positive benefit was observed for all native diseases; however, the magnitude varied slightly by native disease (P = .04) but not by sex (P = .35), age (P = .06), or transplant type (P = .30). In contrast, the SF-36 Mental Component Score did not change from baseline (P = .36) and remained well below population norms.

CONCLUSIONS:

Our results demonstrate that lung transplantation confers clinically important QOL benefits in physical domains but not in psychologic well-being. A better understanding of the barriers to psychologic well-being after transplant is critical to enhancing the benefits of lung transplantation.

  • Baughman RP
  • Meyer KC
  • Nathanson I
  • Angel L
  • Bhorade SM
  • et al.
Chest. 2012 Nov;142(5):e1S-e111S doi: 10.1378/chest.12-1044.
OBJECTIVES:

Immunosuppressive pharmacologic agents prescribed to patients with diffuse interstitial and inflammatory lung disease and lung transplant recipients are associated with potential risks for adverse reactions. Strategies for minimizing such risks include administering these drugs according to established, safe protocols; monitoring to detect manifestations of toxicity; and patient education. Hence, an evidence-based guideline for physicians can improve safety and optimize the likelihood of a successful outcome. To maximize the likelihood that these agents will be used safely, the American College of Chest Physicians established a committee to examine the clinical evidence for the administration and monitoring of immunosuppressive drugs (with the exception of corticosteroids) to identify associated toxicities associated with each drug and appropriate protocols for monitoring these agents.

METHODS:

Committee members developed and refined a series of questions about toxicities of immunosuppressives and current approaches to administration and monitoring. A systematic review was carried out by the American College of Chest Physicians. Committee members were supplied with this information and created this evidence-based guideline.

CONCLUSIONS:

It is hoped that these guidelines will improve patient safety when immunosuppressive drugs are given to lung transplant recipients and to patients with diffuse interstitial lung disease.