Christian A. Merlo

HIV Infection Is Associated with an Increased Risk for Lung Cancer, Independent of Smoking

BACKGROUND Human immunodeficiency virus (HIV)-infected persons have an elevated risk for lung cancer, but whether the increase reflects solely their heavy tobacco use remains an open question. METHODS The Acquired Immunodeficiency Syndrome (AIDS) Link to the Intravenous Experience Study has prospectively observed a cohort of injection drug users in Baltimore, Maryland, since 1988, using biannual collection of clinical, laboratory, and behavioral data. Lung cancer deaths were identified through linkage with the National Death Index. Cox proportional hazards regression was used to examine the effect of HIV infection on lung cancer risk, controlling for smoking status, drug use, and clinical variables. RESULTS Among 2086 AIDS Link to the Intravenous Experience Study participants observed for 19,835 person-years, 27 lung cancer deaths were identified; 14 of the deaths were among HIV-infected persons. All but 1 (96%) of the patients with lung cancer were smokers, smoking a mean of 1.2 packs per day. Lung cancer mortality increased during the highly active antiretroviral therapy era, compared with the pre-highly active antiretroviral therapy period (mortality rate ratio, 4.7; 95% confidence interval, 1.7-16). After adjusting for age, sex, smoking status, and calendar period, HIV infection was associated with increased lung cancer risk (hazard ratio, 3.6; 95% confidence interval, 1.6-7.9). Preexisting lung disease, particularly noninfectious diseases and asthma, displayed trends for increased lung cancer risk. Illicit drug use was not associated with increased lung cancer risk. Among HIV-infected persons, smoking remained the major risk factor; CD4 cell count and HIV load were not strongly associated with increased lung cancer risk, and trends for increased risk with use of highly active antiretroviral therapy were not significant. CONCLUSIONS HIV infection is associated with significantly increased risk for developing lung cancer, independent of smoking status.

Association between respiratory tract methicillin-resistant Staphylococcus aureus and survival in cystic fibrosis

CONTEXT The prevalence of methicillin-resistant Staphylococcus aureus (MRSA) in the respiratory tract of individuals with cystic fibrosis (CF) has increased dramatically; however, its impact on outcomes in CF is unclear. Because the time between infection with bacteria in CF and death can be decades, observational studies with long periods of follow-up are well suited to address the current gap in knowledge. OBJECTIVE To determine whether isolation of MRSA from the respiratory tract of CF patients is associated with worse survival compared with patients who never have a culture positive for MRSA. DESIGN, SETTING, AND PARTICIPANTS Cohort study of 19,833 CF patients aged 6 to 45 years seen at centers accredited by the Cystic Fibrosis Foundation in the United States. Patients entered between January 1996 and December 2006 and were followed up through December 2008. Cox regression models with time-varying covariates were used to compare survival between CF patients with and without respiratory tract MRSA. MAIN OUTCOME MEASURE Time from age at entry until age at death from any cause. RESULTS In 137,819 patient-years of observation (median, 7.3 years/patient), 2537 CF patients died and 5759 patients had MRSA detected. The mortality rate was 18.3 deaths (95% confidence interval [CI], 17.5-19.1) per 1000 patient-years in patients without MRSA and 27.7 deaths (95% CI, 25.3-30.4) per 1000 patient-years in those with MRSA. Among those with MRSA, the attributable risk percentage of death associated with MRSA was 34.0% (95% CI, 26.7%-40.4%). The unadjusted hazard ratio associated with MRSA was 1.47 (95% CI, 1.32-1.62). After adjustment for time-varying covariates associated with severity of illness, MRSA remained associated with a higher risk of death (1.27; 95% CI, 1.11-1.45). CONCLUSION Detection of MRSA in the respiratory tract of CF patients was associated with worse survival.

Persistent methicillin-resistant Staphylococcus aureus and rate of FEV1 decline in cystic fibrosis.

RATIONALE The prevalence in cystic fibrosis (CF) of respiratory cultures with methicillin-resistant Staphylococcus aureus (MRSA) has dramatically increased over the last 10 years, but the effect of MRSA on FEV(1) decline in CF is unknown. OBJECTIVES To determine the association between MRSA respiratory infection and FEV(1) decline in children and adults with CF. METHODS This was a 10-year cohort study using the Cystic Fibrosis Foundation patient registry from 1996-2005. We studied individuals who developed new MRSA respiratory tract infection. Repeated-measures regression was used to assess the association between MRSA and FEV(1) decline, adjusted for confounders, in individuals aged 8-21 years and adults (aged 22-45 yr). Two different statistical models were used to assess robustness of results. MEASUREMENTS AND MAIN RESULTS The study cohort included 17,357 patients with an average follow-up of 5.3 years. During the study period, 1,732 individuals developed new persistent MRSA infection (> or =3 MRSA cultures; average, 6.8 positive cultures) and were subsequently followed for an average of 3.5 years. Even after adjustment for confounders, rate of FEV(1) decline in individuals aged 8-21 years with persistent MRSA was more rapid in both statistical models. Their average FEV(1) decline of 2.06% predicted/year was 43% more rapid than the 1.44% predicted/year in those without MRSA (difference, -0.62% predicted/yr; 95% confidence interval, -0.70 to -0.54; P < 0.001). Effect of MRSA on FEV(1) decline in adults was not clinically significant. CONCLUSIONS Persistent infection with MRSA in individuals with CF between the ages of 8 and 21 years is associated with a more rapid rate of decline in lung function.

An epistaxis severity score for hereditary hemorrhagic telangiectasia.

Hereditary hemorrhagic telangiectasia (HHT)‐related epistaxis leads to alterations in social functioning and quality of life. Although more than 95% experience epistaxis, there is considerable variability of severity. Because no standardized method exists to measure epistaxis severity, the purpose of this study was to determine factors associated with patient‐reported severity to develop a severity score.

Impact of U.S. Lung Allocation Score on Survival After Lung Transplantation

BACKGROUND The Lung Allocation Score (LAS) dramatically changed organ allocation in lung transplantation. The impact of this change on patient outcomes is unknown. The purpose of the study was to examine early mortality after lung transplantation under the LAS system. METHODS All patients undergoing first-time lung transplantation during the period from May 1, 2005 through April 30, 2008 were included in the study. The cohort was divided into quintiles by LAS. A high-risk group (LAS >46) was comprised of the highest quintile, Quintile 5, and a low-risk group (LAS < or =46) included the lower quintiles, Quintiles 1 through 4. A time-to-event analysis was performed for risk of death after transplantation using Kaplan-Meier survival and Cox proportional hazards models. RESULTS There were 4,346 patients who underwent lung transplantation during the study period. Patients in the high-risk group (LAS >46) were more likely to have idiopathic pulmonary fibrosis (IPF; 52.9% vs 23.8%, p < 0.001) and diabetes (25.8% vs 16.8%, p < 0.001) and to require mechanical ventilatory support (15.4% vs 2.2%, p < 0.001) at the time of transplant as compared with patients in the low-risk group. One-year survival using the Kaplan-Meier product limit estimator was significantly worse in the high-risk group (75% vs 83%, p < 0.001 by log-rank test). Patients in the high-risk group were also found to have increased risk of death (hazard ratio 1.46, 95% confidence interval 1.24 to 1.73) compared with the low-risk group. CONCLUSIONS Overall 1-year survival under the new LAS system appears to be similar to that in historic reports. However, risk of death was significantly increased among patients with LAS >46.

The effect of HIV infection on longitudinal lung function decline among IDUs: a prospective cohort.

Objective:As survival with HIV infection improves, HIV-infected individuals appear to be susceptible to development of chronic diseases, including restrictive and obstructive lung diseases. We sought to determine the independent association of HIV infection on lung function decline. Design:Longitudinal analysis of the AIDS Linked to the Intravenous Experience study, an observational cohort of current and former IDUs. Methods:Generalized estimating equations were used to determine the effects of markers of HIV infection on adjusted annual change in forced expiratory volume in one second (FEV1) and forced vital capacity (FVC). Results:A total of 1064 participants contributed 4555 spirometry measurements over a median follow-up time of 2.75 years. The mean age of the cohort was 48 years; nearly, two-thirds were men and 85% current smokers. After adjustment, the overall annual decline of FEV1 and FVC between HIV-infected and uninfected persons did not differ. However, there was a 76 ml/year greater rate of decline in FEV1 and 86 ml/year greater rate of decline in FVC among HIV-infected participants with viral load more than 75 000 copies/ml compared with HIV-uninfected individuals (P < 0.01). Similarly, HIV-infected individuals with CD4 cell count less than 100 cells/&mgr;l had a 57 ml/year more rapid decline in FEV1 and 86 ml/year more rapid decline in FVC than HIV-uninfected participants (P = 0.018 and P = 0.001, respectively). Conclusion:Markers of poorly controlled HIV disease are independently associated with accelerated annual lung function decline, with decrements in both FEV1 and FVC. These findings highlight the need for optimized HIV antiretroviral therapy in addition to smoking cessation among HIV-infected individuals with tobacco dependence.

The impact of recipient body mass index on survival after lung transplantation

BACKGROUND Lung transplant (LTx) candidates are frequently over or underweight. Few studies have examined recipient weight and outcomes after LTx. The United Network for Organ Sharing (UNOS) database provides an opportunity to examine outcomes related to body mass index (BMI) in a large cohort of LTx patients. METHODS The UNOS data set was retrospectively reviewed for 11,411 adult primary LTx patients (1998 to 2008). Patients were stratified by recipient BMI (kg/m(2)): less than 18.5 (underweight), 18.5 to 24.9 (normal), 25.0 to 29.9 (overweight), more than 30 (obese). All-cause mortality was examined with Cox proportional hazard regression incorporating 15 variables. Survival was modeled using the Kaplan-Meier method. RESULTS Of 11,411 recipients, 1,355 (11.9%) were underweight, 4,998 (43.8%) were normal weight, 3,662 (62.1%) were overweight, and 1,396 (12.2%) were obese. During the study, 4,959 patients (43.5%) died. Mortality was significantly different between the strata, with incremental increases in death for each BMI category above or below normal. On multivariable analysis, BMI strata predicted death compared with normal weight. Risk of death was increased in recipients who were underweight (hazard ratio [HR], 1.14; 95% confidence interval [CI], 1.03-1.26; p = 0.01), overweight (HR, 1.06; 95% CI, 0.99-1.14; p = 0.1), and obese (HR, 1.16; 95% CI, 1.04-1.28; p = 0.005). Kaplan-Meier modeling showed a significant effect of BMI on survival; however, this effect was no longer significant when first-year deaths were excluded. CONCLUSIONS Mortality is higher in underweight, overweight, and obese LTx patients than in normal-weight controls. However, this effect appears to be governed by survival in the first year after LTx.

Association between obstructive lung disease and markers of HIV infection in a high-risk cohort

Background Evidence suggests an association between HIV infection and the presence of obstructive lung disease (OLD). However, the associations between specific markers of HIV infection and OLD remain unclear. A study was undertaken to determine the independent associations of HIV infection, CD4 cell count and plasma HIV viral load with the presence of OLD in an urban cohort. Methods Clinical, laboratory and spirometric data from the AIDS Linked to the Intravenous Experience (ALIVE) study, an observational study of current and former injection drug users in Baltimore, Maryland, were analysed. Multivariable logistic regression models were generated to identify HIV infection indices independently associated with OLD. Results Of 1077 participants (mean±SD age 48±8 years), 89% were African-American, 65% were men and 86% were current smokers. A total of 303 (28%) were HIV infected and 176 (16%) had spirometry-defined OLD. Higher viral load was independently associated with OLD. HIV-infected individuals with viral load >200 000 copies/ml had a 3.4-fold increase in the odds of OLD compared with HIV-negative participants (95% CI 1.24 to 9.39; p=0.02). The association between higher HIV viral load and OLD persisted after accounting for antiretroviral therapy use (OR 4.06, 95% CI 1.41 to 11.7; p=0.01). No association was observed between HIV serostatus or CD4 cell count and the presence of OLD. Conclusion In a cohort at risk for OLD and HIV infection, high viral load but not CD4 cell count was associated with an increased prevalence of spirometry-defined OLD. These findings suggest that higher viral load may contribute mechanistically to the increased risk of OLD in patients with HIV infection.

The impact of center volume on survival in lung transplantation: an analysis of more than 10,000 cases.

BACKGROUND Whether center volume influences outcomes in lung transplantation is unknown. We reviewed United Network for Organ Sharing data to examine the effect of center volume on short-term mortality. METHODS We reviewed United Network for Organ Sharing data (1998 through 2007) to identify 10,496 first-time adult lung transplantation recipients at 79 centers. Centers were stratified by quartiles of mean annual volume. Risk of 30-day mortality and 1- and 5-year mortality (censored for 30-day death) were assessed by multivariable Cox proportional hazards regression. RESULTS Mean center volume ranged from less than 1 to 58.2 (median, 9.4 cases/year; volume quartiles: 0 to 2.1, 2.2 to 9.4, 9.5 to 19.9, and 20 to 58.2 cases). Each 1 case/year decrease led to a 2% increase in 30-day mortality (hazard ratio, 1.02; 95% confidence interval, 1.01 to 1.02; p < 0.001). Centers of lowest quartile (performing <or=2.1 lung transplantations/year) had a 30-day cumulative mortality of 9.6% or 89% increase in the risk of death (hazard ratio, 1.89; 95% confidence interval, 1.01 to 3.44; p = 0.05) compared with the highest quartile centers despite fewer idiopathic pulmonary fibrosis patients (15.6% versus 25.8%; p < 0.001) and younger age (40.9 versus 51.5 years; p < 0.001). Low-volume centers had double the risk of 30-day censored 1-year mortality (hazard ratio, 1.95; 95% confidence interval, 1.30 to 2.92; p = 0.001). High-volume centers (>or=20 lung transplantations/year) had the lowest 30-day mortality (4.1%). CONCLUSIONS We provide an initial examination of the relationship of volume and lung allocation score to outcomes for lung transplantation. Low center volume is associated with increased short-term and cumulative mortality despite fewer idiopathic pulmonary fibrosis patients and younger patients.

Cryoprobe Transbronchial Lung Biopsy in Patients After Lung Transplantation: A Pilot Safety Study

BACKGROUND Transbronchial biopsies using standard forceps (FTBBxs) are often limited by crush artifact and their small size. To date, there have been no studies aimed at assessing the safety and efficacy of cryoprobe biopsies (CPBxs) in the population of patients who have undergone lung transplants. We present the safety profile and biopsy results from the fi rst 21 procedures in a pilot study comparing CPBx to FTBBx in patients after lung transplantation. METHODS Patients who had undergone lung transplant and who were scheduled for bronchoscopy were sequentially enrolled between November 2011 and September 2012. Inclusion criteria included age . 18 years and bilateral, orthotopic lung transplant. Exclusion criteria were coagulopathy, FEV 1 < 0.8 L, diffuse bullous disease, hemodynamic instability, and severe hypoxemia (Pa(O2) < 55 mm Hg or Sp(O2) < 92% on room air). Twenty-one procedures were performed, 10 using rigid bronchoscopy followed by 11 via flexible bronchoscopy. Patients were monitored for complications including pneumothorax, hemodynamic instability, and/or respiratory distress. Bleeding was categorized on an adapted grading system. RESULTS Twenty-one procedures in 17 patients (median age: 52 years; 12 male patients) were performed. Specimen area and percent open alveoli were significantly greater using CPBx compared with FTBBx ( P < .05). No clinically significant procedural complications occurred and all patients were discharged the day of the procedure. CONCLUSIONS The use of the cryoprobe is a safe, alternative technique to FTBBx during post-lung transplant bronchoscopy. Further studies are needed to determine if larger samples obtained with CPBx translate to an increased diagnostic yield.