Bright New Resources for Syphilis Research: Genetically Encoded Fluorescent Tags for Treponema pallidum and Sf1Ep Cells.

The recently discovered methodologies to cultivate and genetically manipulate Treponema pallidum subsp. pallidum (T. pallidum) have significantly helped syphilis research, allowing the in vitro evaluation of antibiotic efficacy, performance of controlled studies to assess differential treponemal gene expression, and generation of loss-of-function mutants to evaluate the contribution of specific genetic loci to T. pallidum virulence. Building on this progress, we engineered the T. pallidum SS14 strain to express a red-shifted green fluorescent protein (GFP) and Sf1Ep cells to express mCherry and blue fluorescent protein (BFP) for enhanced visualization. These new resources improve microscopy- and cell sorting-based applications for T. pallidum, better capturing the physical interaction between the host and pathogen, among other possibilities. Continued efforts to develop and share new tools and resources are required to help our overall knowledge of T. pallidum biology and syphilis pathogenesis reach that of other bacterial pathogens, including spirochetes.

Vitamin D and the risk of preeclampsia--a nested case-control study.

We aimed to determine the relation between vitamin D deficiency in early pregnancy and preeclampsia. In a nested case-control study of 2496 pregnant women, we identified 39 women who developed preeclampsia and 120 non-preeclamptic controls. Blood was sampled in 12th gestational week and analyzed for serum vitamin D. Vitamin D levels were similar in women who developed preeclampsia, 52.2 ± 20.5 nmol/L, and controls, 48.6 ± 20.5 nmol/L, p = 0.3. In addition, vitamin D deficiency (<50 nmol/L) was found in a similar proportion of control group (51.7%) as those with severe preeclampsia (41.2%). Women with vitamin D deficiency were 3 cm shorter than those with normal vitamin D levels (p = 0.002). Our data do not support the hypothesis that vitamin D deficiency in early pregnancy is associated with preeclampsia, but we cannot rule out a relation later in gestation.

Bright New Resources for Syphilis Research: Genetically Encoded Fluorescent Tags for Treponema pallidum and Sf1Ep Cells.

The recently discovered methodologies to cultivate and genetically manipulate Treponema pallidum subsp. pallidum ( T. pallidum ) have significantly helped syphilis research, allowing the in vitro evaluation of antibiotic efficacy, performance of controlled studies to assess differential treponemal gene expression, and generation of loss-of-function mutants to evaluate the contribution of specific genetic loci to T. pallidum virulence. Building on this progress, we engineered the T. pallidum SS14 strain to express a red-shifted Green Fluorescent Protein (GFP) and Sf1Ep cells to express mCherry and blue fluorescent protein (BFP) for enhanced visualization. These new resources improve microscopy- and cell sorting-based applications for T. pallidum , better capturing the physical interaction between the host and pathogen, among other possibilities. Continued efforts to develop and share new tools and resources are required to help our overall knowledge of T. pallidum biology and syphilis pathogenesis reach that of other bacterial pathogens, including spirochetes. Graphical abstract: By employing genetic engineering, T. pallidum was modified to express GFP, and Sf1Ep cells to express mCherry on the cytoplasmic membrane and BFP in the nucleus. These new resources for syphilis research will facilitate experimental designs to better define the complex interplay between T. pallidum and the host during infection.

The Antimicrobial Peptide Human Beta-Defensin 2 Inhibits Biofilm Production of Pseudomonas aeruginosa Without Compromising Metabolic Activity.

Biofilm production is a key virulence factor that facilitates bacterial colonization on host surfaces and is regulated by complex pathways, including quorum sensing, that also control pigment production, among others. To limit colonization, epithelial cells, as part of the first line of defense, utilize a variety of antimicrobial peptides (AMPs) including defensins. Pore formation is the best investigated mechanism for the bactericidal activity of AMPs. Considering the induction of human beta-defensin 2 (HBD2) secretion to the epithelial surface in response to bacteria and the importance of biofilm in microbial infection, we hypothesized that HBD2 has biofilm inhibitory activity. We assessed the viability and biofilm formation of a pyorubin-producing Pseudomonas aeruginosa strain in the presence and absence of HBD2 in comparison to the highly bactericidal HBD3. At nanomolar concentrations, HBD2 - independent of its chiral state - significantly reduced biofilm formation but not metabolic activity, unlike HBD3, which reduced biofilm and metabolic activity to the same degree. A similar discrepancy between biofilm inhibition and maintenance of metabolic activity was also observed in HBD2 treated Acinetobacter baumannii, another Gram-negative bacterium. There was no evidence for HBD2 interference with the regulation of biofilm production. The expression of biofilm-related genes and the extracellular accumulation of pyorubin pigment, another quorum sensing controlled product, did not differ significantly between HBD2 treated and control bacteria, and in silico modeling did not support direct binding of HBD2 to quorum sensing molecules. However, alterations in the outer membrane protein profile accompanied by surface topology changes, documented by atomic force microscopy, was observed after HBD2 treatment. This suggests that HBD2 induces structural changes that interfere with the transport of biofilm precursors into the extracellular space. Taken together, these data support a novel mechanism of biofilm inhibition by nanomolar concentrations of HBD2 that is independent of biofilm regulatory pathways.

A randomized trial of inhaled cyclosporine in lung-transplant recipients.

BACKGROUND: Conventional regimens of immunosuppressive drugs often do not prevent chronic rejection after lung transplantation. Topical delivery of cyclosporine in addition to conventional systemic immunosuppression might help prevent acute and chronic rejection events. METHODS: We conducted a single-center, randomized, double-blind, placebo-controlled trial of inhaled cyclosporine initiated within six weeks after transplantation and given in addition to systemic immunosuppression. A total of 58 patients were randomly assigned to inhale either 300 mg of aerosol cyclosporine (28 patients) or aerosol placebo (30 patients) three days a week for the first two years after transplantation. The primary end point was the rate of histologic acute rejection. RESULTS: The rates of acute rejection of grade 2 or higher were similar in the cyclosporine and placebo groups: 0.44 episode (95 percent confidence interval, 0.31 to 0.62) vs. 0.46 episode (95 percent confidence interval, 0.33 to 0.64) per patient per year, respectively (P=0.87 by Poisson regression). Survival was improved with aerosolized cyclosporine, with 3 deaths among patients receiving cyclosporine and 14 deaths among patients receiving placebo (relative risk of death, 0.20; 95 percent confidence interval, 0.06 to 0.70; P=0.01). Chronic rejection-free survival also improved with cyclosporine, as determined by spirometric analysis (10 events in the cyclosporine group and 20 events in the placebo group; relative risk of chronic rejection, 0.38; 95 percent confidence interval, 0.18 to 0.82; P=0.01) and histologic analysis (6 vs. 19 events, respectively; relative risk, 0.27; 95 percent confidence interval, 0.11 to 0.67; P=0.005). The risks of nephrotoxic effects and opportunistic infection were similar for patients in the cyclosporine group and the placebo group. CONCLUSIONS: Inhaled cyclosporine did not improve the rate of acute rejection, but it did improve survival and extend periods of chronic rejection-free survival. (ClinicalTrials.gov number, NCT00268515.).

Roles of T lymphocytes in pulmonary fibrosis.

Infiltration of T lymphocytes in the lungs is common in patients with and in animal models of pulmonary fibrosis. The role of these cells in regulating the accumulation of extracellular matrix, particularly collagen, is not understood completely. Research literature provides evidence for a profibrotic, an antifibrotic, or no significant role of T lymphocytes in pulmonary fibrosis. This review offers a discussion of such evidence with the focus on phenotypes of pulmonary T lymphocytes and related profibrotic and antifibrotic mechanisms. It appears unlikely that T lymphocytic infiltration per se is the central driving force in most cases of pulmonary fibrosis. Instead, evidence suggests that T lymphocytes may modulate the inflammatory and healing responses in the lungs in a profibrotic or antifibrotic manner, depending on their phenotype. Phenotypic reshaping, rather than elimination of the infiltrating pulmonary T lymphocytes, may be a promising approach to improving outcomes in patients with pulmonary fibrosis.

Intrabronchial Catheter Resuscitation for Respiratory and Cardiorespiratory Arrest.

INTRODUCTION: We sought to determine whether intrabronchial oxygenation would provide adequate gas exchange during both anesthesia induced apneic and cardiopulmonary arrest and cardiac massage (CPR). METHODS: Ten pigs underwent general anesthesia with mechanical ventilation. Blood gases were measured in each animal at 4 min intervals for up to 28 min. An intrabronchial catheter (4 L/min O2) was inserted through an endotracheal tube after respirator cessation. Group A animals (6) were resuscitated with the catheter but without CPR. Group B animals (4) were rendered apneic and cardioplegic and resuscitated by CPR for 28 min using the intrabronchial device. RESULTS: All group A animals were resuscitated and survived after 24 min of apnea. Mean pO2 decreased from 378 mmHg (95% confidence interval [CI], 288-468) to 292 mmHg (95% CI, 246-339), P = 0.009; pCO2 increased from 52 mmHg (95% CI, 43-61) to 137 mmHg (95% CI, 116-158), P < 0.0001; and pH decreased from 7.32 (7.29-7.36) to 6.98 (6.92-7.03), P < 0.0001. In a control animal bronchial catheter oxygen flow ceased at baseline and pO2 decreased from 268 to 30 mmHg by 20 min. In group B animals mean pO2 decreased from 426 mmHg (95% CI, 273-579) to 130 mmHg (95% CI, 92-168) after 28 min, P < 0.0001; pCO2 increased from 49 mmHg (95% CI, 41-58) to 73 mmHg (95% CI, 61-86), P = 0.03; and pH decreased from 7.34 (7.33-7.35) to 7.07 (6.98-7.16), P < 0.0001. In the control receiving intratracheal oxygen pO2 decreased from 324 to 88 mmHg after 16 minu of CPR. CONCLUSIONS: Intrabronchial oxygenation provides sustained hyperoxemia during complete apnea and cardiac arrest with CPR.

Evaluation of the electronic version of the questionnaire for lung transplant patients.

UNLABELLED: Context-Recent modifications to the QLTP (Questionnaire for Lung Transplant Patients), including changing items from dichotomous to multiple dimension scaling, adding psychological symptoms, and converting to an electronic format (e-QLTP), made it necessary to reevaluate its reliability, validity, recipient satisfaction, and feasibility of administering the e-QLTP in the clinical setting. Purpose-To report the final modifications, psychometric properties, recipient satisfaction, and feasibility of administering the e-QLTP, a patient report outcome measure of symptoms and activity tolerance. Methods-Sixty lung recipients completed the original QLTP and the e-QLTP and rated their satisfaction with the e-version during a routine posttransplant evaluation; 65% (38 of 60) also completed a retest version. Correlations were computed for retest stability, concurrent validity between versions of the QLTP, and construct validity among the subscales of the e-QLTP and forced expiratory volumes in 1 second. Using the After Scenario Questionnaire, participants rated their satisfaction with the ease, amount of time, and support information when completing the e-QLTP. RESULTS: The e-QLTP and subscales were internally consistent (alpha = .73 - .90) and stable (intraclass correlations = .47 - .93). Significant correlations (P = .001) were found between the e-QLTP and the original QLTP (r = 0.53-0.56) and between the e-QLTP subscales and forced expiratory volumes in 1 second (r = 0.51 - 0.53). The overall mean satisfaction score was 1.27 (+/- 0.47). Conclusions-The e-QLTP is a reliable and valid measure of physical and psychological symptoms after lung transplantation. It is feasible to complete in the clinical setting and recipients are highly satisfied with its use. Its computerized functionality enhances assessment and management of symptoms over time.

Maternal vitamin D deficiency and fetal distress/birth asphyxia: a population-based nested case-control study.

OBJECTIVE: Vitamin D deficiency causes not only skeletal problems but also muscle weakness, including heart muscle. If the fetal heart is also affected, it might be more susceptible to fetal distress and birth asphyxia. In this pilot study, we hypothesised that low maternal vitamin D levels are over-represented in pregnancies with fetal distress/birth asphyxia. DESIGN AND SETTING: A population-based nested case-control study. PATIENTS: Banked sera of 2496 women from the 12th week of pregnancy. OUTCOME MEASURES: Vitamin D levels were analysed using a direct competitive chemiluminescence immunoassay. Vitamin D levels in early gestation in women delivered by emergency caesarean section due to suspected fetal distress were compared to those in controls. Birth asphyxia was defined as Apgar <7 at 5 min and/or umbilical cord pH≤7.15. RESULTS: Vitamin D levels were significantly lower in mothers delivered by emergency caesarean section due to suspected fetal distress (n=53, 43.6±18 nmol/L) compared to controls (n=120, 48.6±19 nmol/L, p=0.04). Birth asphyxia was more common in women with vitamin D deficiency (n=95) in early pregnancy (OR 2.4, 95% CI 1.1 to 5.7). CONCLUSIONS: Low vitamin D levels in early pregnancy may be associated with emergency caesarean section due to suspected fetal distress and birth asphyxia. If our findings are supported by further studies, preferably on severe birth asphyxia, vitamin D supplementation/sun exposure in pregnancy may lower the risk of subsequent birth asphyxia.

Extracorporeal Lung Support as a Bridge to Airway Stenting and Radiotherapy for Airway-Obstructing Pancoast Tumor.

Venovenous (V-V) extracorporeal membrane oxygenation (ECMO) is used for respiratory failure that is suspected to be reversible (bridge to recovery), or as a bridge to lung transplantation. Patients with proximal airway obstruction due to endobronchial malignancy can develop acute respiratory failure, and may benefit from V-V ECMO as a bridge to airway intervention, further treatment, and eventual recovery. We describe a case of a superior sulcus tumor with tracheobronchial and superior vena cava invasion causing both respiratory failure and superior vena cava syndrome. This was treated successfully with V-V ECMO, bronchial stenting, and radiotherapy.

The use of extended criteria donors decreases one-year survival in high-risk lung recipients: A review of the United Network of Organ Sharing Database.

OBJECTIVE: The study objective was to investigate the impact of matching donor quality to recipient severity on survival after lung transplant. METHODS: By using the Organ Procurement and Transplantation Network/United Network for Organ Sharing dataset, we analyzed lung transplant recipients from May 4, 2005, to December 31, 2012. By using adjusted Cox regressions, we identified extended criteria donors as those who had 1 or more of the following: age 65 years or more, smoking history of 20 pack-years or more, diabetes mellitus, or African-American race. All other donors were considered standard donors. Recipients were categorized by lung allocation score: lung allocation score less than 70 and lung allocation score 70 or greater. Our primary outcome was 1-year survival after lung transplantation. RESULTS: Of the 10,995 lung recipients, 3792 (34%) received extended criteria donor organs. Extended criteria donors were associated with an increased hazard of death (hazard ratio [HR], 1.41; 95% confidence interval [CI], 1.26-1.56; P < .001). One-year survival was 87% and 82% (P < .001) for recipients with a lung allocation score less than 70 and 80% and 72% (P = .017) for recipients with a lung allocation score 70 or greater who received standard donor and extended criteria donor organs, respectively. In Cox regression models, the hazard of death was increased for recipients with a lung allocation score less than 70 + extended criteria donor (HR, 1.42; 95% CI, 1.27-1.60; P < .001), recipients with a lung allocation score 70 or greater + standard donor (HR, 1.37; 95% CI, 1.10-1.71; P = .005), and was the highest for recipients with a lung allocation score 70 or greater + extended criteria donor (HR, 1.81; 95% CI, 1.40-2.33; P < .001) compared with recipients with a lung allocation score less than 70 + standard donor. CONCLUSIONS: Extended criteria donors are associated with reduced 1-year survival, and recipients with a lung allocation score 70 or greater who receive extended criteria donor organs have the lowest survival.

p-Cresol and Cardiovascular Risk in Kidney Transplant Recipients.

p-Cresol Sulphate (pCS) is a uremic toxin that originates exclusively from dietary sources and has a high plasma level related to chronic kidney disease (CKD) and cardiovascular disease (CVD). The aim of our study was to evaluate the plasma levels of pCS in kidney transplant recipients (KTRs) related to estimated glomerular filtration rate (eGFR), traditional risk factors, cardiovascular clinical events and endothelial progenitor cells (EPCs), bone marrow-derived cells for the vascular repair system. We considered 51 KTRs and 25 healthy blood donors (HBDs). pCs levels were analyzed using high-performance liquid chromatography (HPLC) coupled with mass spectrometry with an electrospray ionization (ESI) (LC/ESI-MS/MS) on a triple-quadrupole; EPCs were analyzed using flow cytometric analysis. eGFR was 52.61 ± 19.9 mL/min/1.73 m(2) in KTRs versus 94 ± 21 mL/min/1.73 m(2) in HBDs. We did not find differences in pCS levels between KTRs and HBDs. Levels of pCS were inversely related with eGFR in KTRs and pCS levels were significantly lower in KTRs with eGFR <30 mL/min/1.73 m(2) versus eGFR >30 mL/min/1.73 m(2). Furthermore, there was a difference in pCS levels between eGFR <30 mL/min/1.73 m(2) of KTRs compared with HBDs. Levels of pCS were almost significantly influenced by the presence of a previous vascular event and were inversely related with mature EPCs. These findings suggest that KTRs should not have higher CVD risk than HBDs and their physiological vascular repair system appears to be intact. In KTRs the reduction of eGFR also increased pCS levels and reduced EPCs numbers and angiogenesis capacity. In summary, pCS acts as an emerging marker of a uremic state, helping assess the global vascular competence in KTRs.

Venous Thromboembolic Complications of Lung Transplantation: A Contemporary Single-Institution Review.

BACKGROUND: The incidence and consequences of deep venous thrombosis (DVT) and pulmonary embolism (PE) have not been described recently in lung transplant recipients. We sought to characterize DVT and PE in a contemporary series of lung transplant recipients and describe their association with clinical outcomes. METHODS: The records of all lung transplant recipients from July 1, 2008, to June 30, 2013, were reviewed and analyzed. DVT was diagnosed by venous duplex ultrasonography. PE was diagnosed by computed tomography angiography, nuclear ventilation/perfusion scanning, or pulmonary angiography. RESULTS: The study comprised 117 patients who underwent 123 transplants. The median age was 63 years (range, 17 to 77 years). Forty-five patients (39%) had evidence of lower extremity DVT, 53 (45%) had no evidence of lower extremity DVT, and 19 (16%) were not tested. Fifty-three (45%) had evidence of upper extremity DVT, 30 (26%) had no evidence of upper extremity DVT, and 34 (29%) were not tested. Eighteen (15%) had evidence of PE, 82 (70%) had no evidence of PE, and 17 (15%) were not tested. A multivariable, stepwise Cox proportional hazards model revealed that the presence of lower extremity DVT (hazard ratio, 2.43; 95% confidence interval, 1.29 to 4.64), use of cardiopulmonary bypass (hazard ratio, 2.21; 95% confidence interval, 1.04 to 4.68), and unilateral lung transplantation (hazard ratio, 2.13; 95% confidence interval, 1.07 to 4.25) were associated with diminished survival. CONCLUSIONS: The incidence of DVT and PE in lung transplant recipients is high. Posttransplant surveillance and treatment based on findings are warranted.

Pulmonary embolism on postmortem examination: an under-recognized complication in lung-transplant recipients?

INTRODUCTION: Postmortem reports highlight the importance of factors that individually or collectively limit survival. The prevalence of pulmonary embolism (PE) at autopsy in lung-transplant recipients has not been characterized previously. OBJECTIVE: We aimed to describe the prevalence of PE, infection, and acute and chronic rejection at autopsy and their respective contributions to death in lung-transplant recipients according to survival posttransplantation. METHODS: We retrospectively reviewed 126 autopsy reports performed in lung-and heart-lung-transplant recipients between June 1990 and September 2002. RESULTS: PE was identified at autopsy in 34 (27.0%) of 126 lung- and heart-lung-transplant recipients. The prevalence of autopsy-established PE was highest, at 36.4%, in the early group (1-30 days) compared with 20.0% and 23.8% in the intermediate (31-365 days) and late (>365 days) groups, respectively. Although fungal and viral pneumonia were noted most frequently in the early and intermediate groups, bacterial pneumonia was noted in 32% to 45% of autopsies over the posttransplant period. Acute cellular rejection and bronchiolitis obliterans were present in 29.5% and 2.3%, 40.0% and 17.5%, and 35.7% and 42.9% of patients in the early, intermediate, and late groups, respectively. The most frequent cause of death was bacterial infection. CONCLUSIONS: The prevalence of PE was highest in mechanically ventilated lung-transplant recipients in the early postoperative period. Heart-lung recipients were at lower risk for PE compared with double- and single-lung recipients. PE may be an under-appreciated complication contributing to respiratory failure in the early postoperative period.

HLA-specific antibodies are associated with high-grade and persistent-recurrent lung allograft acute rejection.

BACKGROUND: The impact of HLA-specific antibodies is not well established in the acute rejection of lung allografts. Acute rejection represents the most important risk factor for the development of chronic lung allograft dysfunction. METHODS: We analyzed the pattern of HLA antibodies before and after transplantation in 54 patients, and correlated our data with the presence and frequency of high-grade and persistent-recurrent acute rejection, during the first 18 post-operative months. The diagnosis of acute rejection was based on histologic International Society for Heart and Lung Transplantation (ISHLT)-published criteria. RESULTS: Ten of 54 patients had a positive enzyme-linked immunoassay (ELISA) post-transplantation. In 90% of ELISA-positive patients, the presence of HLA antibodies was associated with persistent-recurrent acute rejections, compared with 34% in the ELISA-negative group (p < 0.005). There were 28 high-grade acute rejection episodes in the ELISA-positive group, compared with 36 in the ELISA-negative group (p < 0.0001). The ELISA-positive patients required a greater intensity of immunosuppressive therapy. The patients with ELISA-detected anti-HLA antibodies were at least 3-fold more likely to develop high-grade acute rejection and persistent-recurrent acute rejection, and 7-fold more likely to develop multiple episodes of persistent-recurrent acute rejection, compared with ELISA-negative patients. CONCLUSIONS: ELISA-based screening for the development of HLA antibodies is a reliable method that can identify lung transplant recipients at increased risk for high-grade and persistent-recurrent acute rejection. Although bronchiolitis obliterans appears as a point of no return in the evolution of lung-transplanted patients, early detection of risk factors for acute rejection could indirectly decrease the incidence of bronchiolitis obliterans. These lung-transplanted patients may benefit from an altered strategy of immunosuppression.

Endobronchial metallic stent placement for airway complications after lung transplantation: longitudinal results.

BACKGROUND: In lung transplant recipients, bronchial stenosis (SB) and bronchomalacia (MB) result in obstructive airway disease and allograft dysfunction due to pulmonary infection. We hypothesized that endobronchial metallic stent placement for SB and MB would result in long-term improvement in respiratory function and rates of pulmonary infection. METHODS: We studied symptomatic lung transplant recipients with bronchoscopic evidence of proximal airway complications (SB or MB) and a synchronous decline in forced expiratory volume in 1 second (FEV1) of at least 10% in the 6-month period before intervention. Stent placement was the primary intervention for SB and all focal MB lesions and for recurrent or refractory SB lesions failing a single initial attempt at balloon dilation. FEV1 and rates of pulmonary infection were assessed in the 12-month interval before and after stent placement. Spirometric evaluation was performed at 3-month intervals and compared with spirometry at the time of stent placement. The rates of pulmonary infection, determined by the number of antibiotics prescribed, was determined before and after endobronchial correction. RESULTS: Thirty recipients underwent a total of 75 procedures (50 stent insertions and 25 balloon dilations). FEV1 improved significantly after stent placement compared with base line (1.29 +/- 0.43 L) as follows: 3 months, 1.45 +/- 0.50 L, p = 0.014; 6 months, 1.59 +/- 0.57 L, p = 0.002; 12 months 1.59 +/- 0.53 L, p = 0.006. The infection rate decreased from the 12-month period preceding stent insertion to the corresponding period after stent insertion (6.97/100 days +/- 6.33 versus 5.74/100 days +/- 7.76, p = 0.018). Recurrent SB occurred in 17.3%. No life-threatening complications occurred after stent placement and no deaths were attributed to stent malfunction or malposition. CONCLUSIONS: In lung transplant recipients with SB and MB, maintenance of airway patency by stent placement is safe and resulted in improvements in lung function and reduced pulmonary infection rates for up to 1 year after their insertion.

Pattern and predictors of early rejection after lung transplantation.

BACKGROUND: Most lung transplant recipients experience improvement in their underlying pulmonary condition but are faced with the threat of allograft rejection, the primary determinant of long-term survival. Several studies examined predictors of rejection, but few focused on the early period after transplantation. OBJECTIVES: To describe the pattern and predictors of early rejection during the first year after transplantation to guide the development of interventions to facilitate earlier detection and treatment of rejection. METHODS: Data for donor, recipient, and posttransplant variables were retrieved retrospectively for 250 recipients of single or double lung transplants. RESULTS: Most recipients (85%) had at least 1 episode of acute rejection; 33% had a single episode; 23% had recurrent rejection; 3% had persistent rejection; 13% had refractory rejection; and 14% had clinicopathological evidence of chronic rejection. Serious rejection (refractory acute rejection or chronic rejection) developed in 27% of recipients. Compared with other recipients, recipients who had serious rejection had more episodes of acute rejection (P = .004), and the first acute episodes occurred sooner after transplantation (P = .01) and were of a higher grade (P = .002). CONCLUSIONS: Recipients who experienced higher grades for their first episode of acute rejection (P = .03) and higher cumulative rejection scores (P = .004) were significantly more likely than other recipients to have serious rejection during the first year after transplantation.

Are symptom reports useful for differentiating between acute rejection and pulmonary infection after lung transplantation?

BACKGROUND: Prompt treatment of acute rejection and pulmonary infection reduces morbidity and mortality in lung transplant recipients. Symptoms, spirometry, and bronchoscopy are used to detect these complications. Of these, symptom reporting is the least invasive, yet has received little critical examination. OBJECTIVE: To examine the potential for using reports of symptoms, such as cough and shortness of breath, to recognize clinically significant acute rejection and pulmonary infection after lung transplantation. METHODS: Symptoms reported during routine follow-up visits were compared between lung transplant recipients (LTR) with clinically significant acute rejection (grade >or= A2) and those without (grade A0 or A1) and between LTR with rejection (grade >or= A2) and those with pulmonary infection. RESULTS: LTR with rejection (grade >or= A2) reported more symptoms (P < .01) than did those without (grade A0, A1); however, the magnitude of difference was minimal. LTR with clinically significant acute rejection (grade >or= A2) reported symptoms at a rate comparable with those having pulmonary infection. CONCLUSIONS: Although symptoms may alert LTR to changes in their condition, no symptoms (respiratory, general, or activities of daily living [ADL]) differentiate between grades of rejection or pulmonary infection.

Evaluating the reliability and validity of the Questionnaire for Lung Transplant Patients.

CONTEXT: The Questionnaire for Lung Transplant Patients was designed for clinical use by the pulmonary transplant team in the routine evaluation of lung transplant recipients. Using the self-administered questionnaire, recipients check symptoms that they have had since their last evaluation and rate their shortness of breath, cough, and activity tolerance. OBJECTIVE: To determine whether the questionnaire meets reliability and validity standards for empirical measurement. METHODS: Demographics and disease-severity characteristics were examined in a cross-sectional survey of 37 recipients. Test-retest and intraclass correlation methods were used to estimate stability, and the Cronbach alpha was used to estimate internal consistency. Criterion validity was examined by using The Modified Symptom Frequency/Symptom Distress Scale, Functional Performance Inventory, and visual analog scales for cough and shortness of breath as criterion measures. Construct validity was examined to assess the predicted negative correlation between symptoms and functional performance. RESULTS: The questionnaire and its subscales were internally consistent (Cronbach alpha = 0.82, 0.76, 0.80, and 0.96), and the questionnaire was stable (r = 0.70) and reliable (intraclass correlations = 0.80 and 0.90). Significant correlations were found between the questionnaire and all criterion measures (r = 0.50-0.93). Significant correlations in the predicted negative direction were found between the respiratory subscale and functional performance (r = -0.51) and between cough (r = -0.51) and shortness of breath (r = -0.68) ratings and functional performance. CONCLUSIONS: The Questionnaire for Lung Transplant Patients is reliable and valid, and it provides scientifically sound information for clinical and empirical evaluation of symptoms and their effects on activity tolerance after lung transplantation.

Using conceptual triangulation to develop an integrated model of the symptom experience of acute rejection after lung transplantation.

The aim of this study was to develop a comprehensive model of the symptom experience associated with the development of acute rejection after lung transplantation by integrating the findings from a theory-testing quantitative study that explored the physiologic aspects and a theory-generating qualitative study that explored the interpretive aspects. Findings from the multimethod studies were integrated using conceptual triangulation methods described by Foster (Adv Nurs Sci. 1997;20:1-12). The integrated model will guide the development of interventions to promote effective patterns of symptom recognition and reporting of acute rejection.