A. Whitney Brown

Pulmonary artery size as a predictor of pulmonary hypertension and outcomes in patients with chronic obstructive pulmonary disease

RATIONALE The relationship between pulmonary artery size with underlying pulmonary hypertension and mortality remains to be determined in COPD. We sought to evaluate the relationships in a cohort of patients with advanced COPD. METHODS A retrospective study of advanced COPD patients evaluated between 1998 and 2012 was conducted at a tertiary care center. Patients with chest computed tomography images and right heart catheterizations formed the study cohort. The diameters of the pulmonary artery and ascending aorta were measured by independent observers and compared to pulmonary artery pressures. Intermediate-term mortality was evaluated for the 24-month period subsequent to the respective studies. Cox proportional hazards model was used to determine independent effects of variables on survival. RESULTS There were 65 subjects identified, of whom 38 (58%) had pulmonary hypertension. Patients with and without pulmonary hypertension had mean pulmonary artery diameters of 34.4 mm and 29.1 mm, respectively (p = 0.0003). The mean PA:A ratio for those with and without pulmonary hypertension was 1.05 and 0.87, respectively (p = 0.0003). The PA:A ratio was an independent predictor of mortality with a reduced survival in those with a PA:A >1 (p = 0.008). CONCLUSIONS The PA:A ratio is associated with underlying pulmonary hypertension in patients with COPD and is an independent predictor of mortality. This readily available measurement may be a valuable non-invasive screening tool for underlying pulmonary hypertension in COPD patients and appears to impart important independent prognostic information.

The Red Cell Distribution Width as a Prognostic Indicator in Idiopathic Pulmonary Fibrosis

BACKGROUND The course of idiopathic pulmonary fibrosis (IPF) is characterized by variable patterns of disease progression. The red cell distribution width (RDW) is a parameter that is routinely reported with all CBC counts. We sought to test the prognostic usefulness of this parameter in a well-defined cohort of patients with IPF. METHODS CBCs, demographics, and pulmonary function data from patients with IPF evaluated between January 1997 and June 2011 were collated. Patient outcomes were ascertained from the programs database and the Social Security Death Index. RESULTS There were 319 patients with IPF evaluated in whom baseline CBCs were available. The range in the RDW was 11.9 to 21.9 (median 14.1). There were 228 subjects with RDW values ≤ 15 (normal) and 91 patients with RDW values > 15. Patients with normal RDW values had a median survival of 43.1 months compared with 16.3 months for those whose RDW was > 15 (P = .001). There were 198 patients with available serial RDW data. Those patients who had a change in the RDW of less or greater than +0.010/mo had median survivals of 43.0 and 23.9 months, respectively (P = .0246). CONCLUSIONS The RDW is a readily available laboratory test result that may provide important, independent prognostic information at baseline and follow-up in patients with IPF. Further studies are warranted to validate this as a biomarker for IPF outcomes, as well as to define the biologic basis for this association.

Lung transplantation in IIP: A review

The idiopathic interstitial pneumonias (IIP) encompass a large and diverse subtype of interstitial lung disease (ILD) with idiopathic pulmonary fibrosis (IPF) and non‐specific interstitial pneumonia (NSIP) being the most common types. Although pharmacologic treatments are available for most types of IIP, many patients progress to advanced lung disease and require lung transplantation. Close monitoring with serial functional and radiographic tests for disease progression coupled with early referral for lung transplantation are of great importance in the management of patients with IIP. Both single and bilateral lung transplantation are acceptable procedures for IIP. Procedure selection is a complex decision influenced by multiple factors related to patient, donor and transplant centre. While single lung transplant may reduce waitlist time and mortality, the long‐term outcomes after bilateral lung transplantation may be slightly superior. There are numerous complications following lung transplantation including primary graft dysfunction, chronic lung allograft dysfunction (CLAD), infections, gastroesophageal reflux disease (GERD) and airway disease that limit post‐transplant longevity. The median survival after lung transplantation is 4.7 years in patients with ILD, which is less than in patients with other underlying lung diseases. Although long‐term survival is limited, this intervention still conveys a survival benefit and improved quality of life in suitable IIP patients with advanced lung disease and chronic hypoxemic respiratory failure.

Dynamic Patient Counseling: A Novel Concept in Idiopathic Pulmonary Fibrosis

BACKGROUND The characteristics of long-term survivors with idiopathic pulmonary fibrosis (IPF) have never been fully elucidated. We sought to illustrate the attenuated mortality and describe the characteristics of patients with IPF who survived at least 5 years beyond their initial presentation. METHODS Patients with IPF evaluated between 1997 and 2006 were identified through the clinic database. Patients who survived beyond 5 years from the time of their evaluation were compared with those who died or underwent lung transplantation within 5 years. Survival analyses were performed from the time of initial evaluation and contingent on annualized survival thereafter. RESULTS Eighty-seven patients who survived at least 5 years formed the comparator group to whom other patients were contrasted. These patients had a higher BMI, FVC % predicted, FEV1 % predicted, total lung capacity % predicted, and diffusing capacity of lung for carbon monoxide % predicted, but a lower FEV1/FVC ratio and lower mean pulmonary artery pressures. More than one-half of these patients had moderate or severe disease at the time of presentation. Our annualized contingent survival analyses revealed a progressively increasing median survival dependent on the duration of the disease. CONCLUSIONS Although we were able to demonstrate differences in our 5-year survivors, rather than being a distinct group, these patients appear to exist within a continuum of improving survival dependent on prior disease duration. This progressively improving time-dependent prognosis mandates the serial reevaluation of an individual patient’s projected outcomes. The implementation of dynamic counseling is an important concept in more accurately predicting life expectancy for patients with IPF who are frequently haunted by the prospects of a dismal survival.

Effect of Recombinant Human Pentraxin 2 vs Placebo on Change in Forced Vital Capacity in Patients With Idiopathic Pulmonary Fibrosis: A Randomized Clinical Trial

Importance Idiopathic pulmonary fibrosis (IPF) is a progressive fibrotic lung disease with poor prognosis. Approved therapies do not halt disease progression. Objective To determine the effect of recombinant human pentraxin 2 vs placebo on change from baseline to week 28 in mean forced vital capacity (FVC) percentage of predicted value. Design, Setting, and Participants Phase 2, randomized, double-blind, placebo-controlled trial conducted at 18 sites in 7 countries of eligible patients with IPF (N = 117; aged 40-80 years; FVC ≥50% and ⩽90% predicted; ratio of forced expiratory volume in the first second/FVC >0.70; diffusing capacity for carbon monoxide [DLCO] ≥25% and ⩽90% predicted; and distance of ≥150 m on the 6-minute walk test). Study period was August 2015-May 2017. Interventions Patients were randomized to receive either recombinant human pentraxin 2 (10 mg/kg intravenous every 4 weeks, n = 77) or placebo (n = 39) for 24 weeks, and stratified by concurrent IPF treatment status. Main Outcomes and Measures The primary end point was the least-squares mean change in FVC percentage of predicted value from baseline to week 28 (minimal clinically important difference, decline of 2%-6%). Secondary end points included mean change in lung volumes (total, normal, and interstitial lung abnormalities) on high-resolution computed tomography (HRCT) and 6-minute walk distance (minimal clinically important difference, 24-45 m). Results Of 117 randomized patients, 116 received at least 1 dose of study drug (mean age, 68.6 years; 81.0% men; mean time since IPF diagnosis, 3.8 years), and 111 (95.7%) completed the study. The least-squares mean change in FVC percentage of predicted value from baseline to week 28 in patients treated with recombinant human pentraxin 2 was −2.5 vs −4.8 for those in the placebo group (difference, +2.3 [90% CI, 1.1 to 3.5]; P = .001). No significant treatment differences were observed in total lung volume (difference, 93.5 mL [90% CI, −27.7 to 214.7]), quantitative parenchymal features on HRCT (normal lung volume difference, −1.2% [90% CI, −4.4 to 1.9]; interstitial lung abnormalities difference, 1.1% [90% CI, −2.2 to 4.3]), or measurement of DLCO (difference, −0.4 [90% CI, −2.6 to 1.7]). The change in 6-minute walk distance was −0.5 m for patients treated with recombinant human pentraxin 2 vs −31.8 m for those in the placebo group (difference, +31.3 m [90% CI, 17.4 to 45.1]; P < .001). The most common adverse events in the recombinant human pentraxin 2 vs placebo group were cough (18% vs 5%), fatigue (17% vs 10%), and nasopharyngitis (16% vs 23%). Conclusions and Relevance In this preliminary study, recombinant human pentraxin 2 vs placebo resulted in a slower decline in lung function over 28 weeks for patients with idiopathic pulmonary fibrosis. Further research should more fully assess efficacy and safety. Trial Registration clinicaltrials.gov Identifier: NCT02550873

The Value and Application of the 6-Minute-Walk Test in Idiopathic Pulmonary Fibrosis

&NA; The 6‐minute‐walk test is a commonly used assessment of performance ability in a variety of cardiopulmonary diseases. It provides important functional information that is not captured in standardized pulmonary function testing. The test may be influenced by factors other than the severity of lung disease, including frailty, deconditioning, and musculoskeletal issues. The primary output measure from the 6‐minute‐walk test is the distance walked, which appears to confer prognostic information in many diverse disease states. The 6‐minute‐walk test distance has served as a primary endpoint in many drug trials, most notably in the field of pulmonary arterial hypertension, and to a lesser extent in idiopathic pulmonary fibrosis (IPF). Although the 6‐minute‐walk test has been used in clinical practice and research trials of IPF, there are no specific guidelines regarding its implementation in this growing patient population. Given that there is increasing evidence and experience with its use in clinical trials, development of nuanced standards designed specifically for IPF are much needed. This review touches on a number of complex and crucial issues in the application of this test and provides a framework for future development of 6‐minute‐walk test guidelines customized for IPF.

Pulmonary Hypertension in Diffuse Parenchymal Lung Diseases

&NA; Pulmonary hypertension (PH) can be triggered by any number of disease processes that result in increased pulmonary vascular resistance. Although historically associated with idiopathic pulmonary arterial hypertension (PAH), most patients with PH do not have the idiopathic subtype, but rather PH associated with another underlying diagnosis, such as left heart or lung disease. The World Health Organization (WHO) classification of PH helps conceptualize the different categories based on presumed etiology. WHO group 3 is PH associated with lung disease. This review focuses on PH in diffuse parenchymal lung diseases (DPLDs), such as the idiopathic interstitial pneumonias and other more rare forms of DPLD. Although there are clear associations of PH with DPLD, the exact pathophysiologic mechanisms and full clinical significance remain uncertain. Treatment of PH related to DPLD remains investigational, but an area of great interest given the negative prognostic implications and the growing number of available pulmonary vasoactive agents.

Early postoperative management after lung transplantation: Results of an international survey

Little data exist regarding optimal therapeutic strategies postoperatively after lung transplant (LTx). Current practice patterns rely on expert opinion and institutional experience resulting in nonuniform postoperative care. To better define current practice patterns, an international survey of LTx clinicians was conducted.

Hypertonic saline has a prolonged effect on mucociliary clearance in adults with cystic fibrosis

BACKGROUND Inhaled hypertonic saline (HS) has been shown to increase mucociliary clearance (MCC) and improve clinical outcomes in adults and adolescents with cystic fibrosis (CF). However, in younger children with CF, a large study failed to demonstrate clinical benefits. This discrepancy could reflect pharmacodynamic differences in the MCC response to HS in different populations. We previously demonstrated the absence of a sustained effect of HS on MCC in healthy adults and in this study sought to characterize the durability of the MCC response to HS in adults with CF. METHODS At two study sites, MCC was measured in CF adults using gamma scintigraphy during three separate visits: at baseline, 15 min, and 4 h after a single dose of HS (7% NaCl, 4 mL). Particle clearance rates at these visits were used to assess the durability of the MCC response to HS. RESULTS The average 90-minute clearance rate measured 4 h after HS was significantly increased (21.81% ± 12.8) when compared to baseline (13.77% ± 8.7, p = .048) and showed no apparent slowing relative to the rate measured 15 min after HS. While not all subjects responded to HS, the acute response strongly predicted the sustained effect in these subjects (r = 0.896, p < .0001). CONCLUSIONS These results suggest that, in contrast to healthy adults, a single dose of HS has a prolonged effect on MCC in adults with CF, which lasts at least 4 h. This may explain its clinical efficacy in this population.

Exercise pulmonary haemodynamic response predicts outcomes in fibrotic lung disease

Pulmonary hypertension is diagnosed by an elevated mean pulmonary arterial pressure (mPAP) during resting right heart catheterisation (RHC) [1]. Although “exercise-induced pulmonary hypertension” is no longer a distinct clinical entity, recently, there has been renewed interest in the prognostic value of pulmonary haemodynamic responses to exercise, particularly in patients with fibrotic lung disease [1–4]. As the optimal use of exercise RHC in this cohort remains unknown, our main objective in this study was to study the relationship between exercise haemodynamics and outcomes in fibrotic lung disease patients [3–7]. Haemodynamic changes with exercise, including ΔmPAP/ΔCO, predict clinical worsening in fibrotic lung disease patients http://ow.ly/uKno30lb5fF