Dataset Information

Angiotensin-converting enzyme inhibitors may affect pulmonary function in lymphangioleiomyomatosis.

ABSTRACT:

Introduction

A local renin-angiotensin system exists in the pulmonary nodules of lymphangioleiomyomatosis patients. Sirolimus, the standard treatment for lymphangioleiomyomatosis, stabilizes lung function, but all patients do not respond to or tolerate sirolimus. As renin-angiotensin systems may affect tumor growth and metastasis, we questioned if angiotensin-converting enzyme inhibitors affected lymphangioleiomyomatosis disease progression.

Methods

Retrospective study of 426 patients was performed, examining angiotensin-converting enzyme levels, pulmonary function data, and angiotensin-converting enzyme inhibitor treatment.

Results

Serum angiotensin-converting enzyme levels were elevated in approximately 33% of patients, increased with duration of disease, and were inversely correlated with pulmonary function. Levels decreased significantly over time with sirolimus treatment. Treatment with angiotensin-converting enzyme inhibitors was reported by approximately 15% of patients and was significantly associated with a slower rate of decline in percentage predicted forced expiratory volume (FEV1) and diffusing capacity of the lungs for carbon monoxide (DLCO) in patients not treated with sirolimus. No significant differences in rates of decline of FEV1 or DLCO were seen in patients treated with both inhibitors and sirolimus versus sirolimus alone.

Conclusions

Angiotensin-converting enzyme inhibitors may slow decline of pulmonary function in patients with lymphangioleiomyomatosis not treated with sirolimus. These inhibitors may be an option or adjunct in the treatment of lymphangioleiomyomatosis. A clinical trial may be warranted to examine this possibility.

Funding

NIH.

SUBMITTER: Steagall WK

PROVIDER: S-EPMC6483501 | biostudies-literature | 2019 Mar

REPOSITORIES: biostudies-literature

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Publications

Angiotensin-converting enzyme inhibitors may affect pulmonary function in lymphangioleiomyomatosis.

Steagall Wendy K WK Stylianou Mario M Pacheco-Rodriguez Gustavo G Moss Joel J

JCI insight 20190307 5

<h4>Introduction</h4>A local renin-angiotensin system exists in the pulmonary nodules of lymphangioleiomyomatosis patients. Sirolimus, the standard treatment for lymphangioleiomyomatosis, stabilizes lung function, but all patients do not respond to or tolerate sirolimus. As renin-angiotensin systems may affect tumor growth and metastasis, we questioned if angiotensin-converting enzyme inhibitors affected lymphangioleiomyomatosis disease progression.<h4>Methods</h4>Retrospective study of 426 pati ...[more]

PMID: 30843885

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Project description:ImportanceThe renin-angiotensin system has been implicated in mood disorders. Angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) are among the most commonly used medications, yet their effects on mental health outcomes, particularly suicide, are poorly understood. This study examined the association between suicide and exposure to ACEIs and ARBs. Because of differences in their mode of action, it was speculated that ARBs would be associated with a higher risk of suicide than ACEIs.ObjectiveTo examine the association between suicide and exposure to ARBs compared with ACEIs.Design, setting, and participantsThis population-based nested case-control study of individuals aged 66 years and older used administrative claims databases in Ontario, Canada, from January 1, 1995, to December 31, 2015. Data analysis was performed from January to April 2019. Cases were individuals who died by suicide within 100 days of receiving an ACEI or ARB. The date of death served as the index date. For each case, 4 controls were identified and matched by age (within 1 year), sex, and presence of hypertension and diabetes. All individuals received an ACEI or ARB within 100 days before the index date.ExposuresUse of an ACEI or ARB.Main outcomes and measuresConditional logistic regression was used to estimate odds ratios for the association between suicide and exposure to ARBs compared with ACEIs.ResultsNine hundred sixty-four cases were matched to 3856 controls. The median (interquartile range) age of cases and controls was 76 (70-82) years. Most cases (768 [79.7%]) and controls (3068 [79.6%]) were men. Among cases, 260 (26.0%) were exposed to ARBs, and 704 (18.4%) were exposed to ACEIs. Among controls, 741 (74.0%) were exposed to ARBs, and 3115 (81.6%) were exposed to ACEIs. Compared with ACEI exposure, ARB exposure was associated with higher risk of death by suicide (adjusted odds ratio, 1.63; 95% CI, 1.33-2.00). The findings were consistent in a sensitivity analysis excluding individuals with a history of self-harm (odds ratio, 1.60; 95% CI, 1.29-1.98).Conclusions and relevanceThe use of ARBs may be associated with an increased risk of suicide compared with ACEIs. Preferential use of ACEIs over ARBs should be considered whenever possible, particularly in patients with severe mental health illness.

Project description:BackgroundAngiotensin-converting enzyme inhibitors (ACEis) and angiotensin receptor blockers (ARBs) are widely used in peritoneal dialysis (PD) patients, yet controversy exists about their impact on residual kidney function.ObjectivesThis review aimed to evaluate the benefits and harms of ACEis and ARBs for preserving residual kidney function in PD patients.Search methodsThe Cochrane Renal Group's specialised register, Cochrane Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE (OvidSP interface), Chinese Biomedical Literature Database (CBM), China National Knowledge Infrastructure (CNKI) and other resources were searched by applying a prespecified comprehensive search strategy. Date of last search: 01 May 2014.Selection criteriaRandomised controlled trials (RCTs) and quasi-RCTs comparing ACEis or ARBs with placebo, other antihypertensive drugs or each other in PD patients were included.Data collection and analysisScreening, selection, data extraction and quality assessments for each retrieved article were carried out by two authors using standardised forms. Authors were contacted when published data were incomplete. Statistical analyses were performed using the random effects model and results expressed as risk ratio (RR) with 95% confidence intervals (CI). Heterogeneity among studies was explored using the Cochran Q statistic and the I² test, subgroup analyses and random effects meta-regression.Main resultsSix open-label studies (257 patients) were identified. One study compared ACEi with other antihypertensive drugs, three compared ARBs with other antihypertensive drugs, and two studies compared an ARB with an ACEi. Long-term use (≥ 12 months) of an ARB showed significantly benefit of preserving residual kidney function in continuous ambulatory PD (CAPD) patients (MD 1.11 mL/min/1.73 m², 95% CI 0.38 to 1.83), although there was no significant benefit when an ARB were used short-term (≤ six months). One study showed that compared with other antihypertensive drugs, long-term use (12 months) of the ACEi ramipril showed a significant reduction in the decline of residual kidney function in patients on CAPD (MD -0.93 mL/min/1.73m², 95% CI -0.75 to -0.11), and delayed the progression to complete anuria (RR 0.64, 95% CI 0.41 to 0.99). There was no significant difference in serum potassium, urinary protein excretion, Kt/V, weekly creatinine clearance and blood pressure for ARBs versus other antihypertensive drugs. Compared with other antihypertensive drugs, ramipril showed no difference in mortality and cardiovascular events. Compared with an ACEi, ARBs did not show any difference in residual kidney function.The selection bias assessment was low in four studies and unclear in two. Five studies were open-label; however the primary outcome (residual kidney function) was obtained objectively from laboratory tests, and were not likely to be influenced by the lack of blinding. Reporting bias was unclear in all six studies.Authors' conclusionsCompared with other antihypertensive drugs, long-term use (≥ 12 months) of ACEis or ARBs showed additional benefits of preserving residual kidney function in CAPD patients. There was no significant difference on residual kidney function preservation between ARBs and ACEis. However, limited by the small number of RCTs enrolling small number of participants, there is currently insufficient evidence to support the use of an ACEi or an ARB as first line antihypertensive therapy in PD patients.

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Dataset Information

Angiotensin-converting enzyme inhibitors may affect pulmonary function in lymphangioleiomyomatosis.

Introduction

Methods

Results

Conclusions

Funding

Publications

Angiotensin-converting enzyme inhibitors may affect pulmonary function in lymphangioleiomyomatosis.

Similar Datasets

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