Long-term Course and Prognosis of Idiopathic Pulmonary Fibrosis in the Modern Era

The American Thoracic Society and European Respiratory Society guidelines for the diagnosis and treatment of idiopathic pulmonary fibrosis (IPF) have been published recently. However, the influence, practical application, and utility of the prior consensus statement for IPF have never been evaluated. Demographics, diagnostic criteria, pulmonary function data, and disposition of patients with IPF evaluated at an interstitial lung disease center between 2000 and 2009 were analyzed. Enrollment in clinical drug trials, lung transplantation, and mortality also were assessed. A total of 521 patients with IPF were evaluated, with pulmonary function testing available in 446. In the 64% of patients without surgical lung biopsy, the most common major criterion not fulfilled was bronchoscopy. Lung transplantation was performed in 16.1% of patients, whereas 27.4% of prescreened patients were enrolled in a prospective drug study. Patients with mild, moderate, and severe disease categorized by FVC % predicted had median survivals of 55.6, 38.7, and 27.4 months, respectively. The attrition rate of patients who survived beyond 5 years was attenuated in subsequent years. IPF remains a deadly disease with a poor prognosis. Bronchoscopy does not appear to be required for an accurate diagnosis. A minority of patients were accommodated within a clinical trial or with transplantation. Categorization by baseline FVC % predicted effectively discriminates groups with different long-term outcomes. Our analysis supports the view that the value of statements also can be realized in the subsequent demonstration of their impact on patient management, which might enable further refinements in a continuous, iterative rediscovery process….

Parameters of donor-recipient mismatch and survival after bilateral lung transplantation

BACKGROUND:
The purpose of this study was to investigate the relationship between donor-recipient height, gender and predicted estimates of total lung capacity (pTLC) mismatches and post-transplant survival. METHODS:
The lung transplant databases at three programs were reviewed. The pTLC ratios (donor pTLC/recipient pTLC) and height ratios (donor height/recipient height) were calculated retrospectively. Patients were grouped according to pTLC ratio ≤1.0 or >1.0 and height ratio ≤1.0 or >1.0, and according to gender (mis-)matching. A time-to-event analysis was performed for risk of death after transplantation conditional on 30-day survival using Kaplan-Meier survival and Cox proportional hazard models. RESULTS:
There were 211 adult bilateral lung transplant recipients who qualified for the analysis. Mean follow-up was comparable for all cohorts (range 2.21 to 3.85 years). In the univariate Cox proportional hazard models, a pTLC ratio >1.0 (HR 0.43, p = 0.002) and a height ratio >1.0 (HR 0.61, p = 0.03) were associated with better survival, and a female-donor-to-male-recipient gender mismatch (F-to-M) was associated with worse survival (HR 2.35, p = 0.01). In the multivariate Cox proportional hazard model accounting for F-to-M gender mismatch and height ratio >1.0, a pTLC ratio >1.0 remained associated with survival (HR 0.38, p = 0.015). However, accounting for a pTLC ratio >1.0, a height ratio of >1.0 and F-to-M mismatch were not associated with survival. CONCLUSIONS:
A pTLC ratio >1.0 is associated with improved survival after bilateral lung transplantation. The pTLC ratio might better reflect allograft-thorax mismatch than the height ratio, as it also accounts for effects of gender on lung…

Lung Size Mismatch in Bilateral Lung Transplantation Is Associated With Allograft Function and Bronchiolitis Obliterans Syndrome

BACKGROUND:
Size mismatch between donor lungs and a recipient thorax could affect the major determinants of maximal expiratory airflow: airway resistance, propensity of airways to collapse, and lung elastic recoil. METHODS:
A retrospective review of 159 adults who received bilateral lung transplants was performed. The predicted total lung capacity (pTLC) for donors and recipients was calculated based on sex and height. Size matching was represented using the following formula: pTLC ratio = donor pTLC / recipient pTLC. Patients were grouped according to those with a pTLC ratio > 1.0 (oversized) or those with a pTLC ratio ≤ 1.0 (undersized). Allograft function was analyzed in relation to the pTLC ratio and to recipient and donor predicted function. RESULTS:
The 96 patients in the oversized cohort had a mean pTLC ratio of 1.16 ± 0.13 vs 0.89 ± 0.09 in the 63 patients of the undersized group. At 1 to 6 months posttransplant, the patients in the oversized cohort had higher FEV(1)/FVC ratios (0.895 ± 0.13 vs 0.821 ± 0.13, P < .01) and lower time constant estimates of lung emptying (0.38 ± 0.2 vs 0.64 ± 0.4, P < .01) than patients in the undersized cohort. Although the FVCs expressed as % predicted for the recipient were not different between cohorts, the FVCs expressed as % predicted for the donor organ were lower in the oversized cohort compared with the undersized cohort (at 1-6 months, 52.4% ± 17.1% vs 65.3% ± 18.3%, P < .001). Kaplan-Meier estimates for the occurrence of bronchiolitis obliterans syndrome...

Pulmonary Complications of Lung Transplantation

Lung transplantation is an effective treatment option for select patients with a variety of end-stage lung diseases. Although transplant can significantly improve the quality of life and prolong survival, a myriad of pulmonary complications may result in significant morbidity and limit long-term survival. The recognition and early treatment of these complications is important for optimizing outcomes. This article provides an overview and update of the pulmonary complications that may be commonly encountered by pulmonologists caring for these patients. …

Parenchymal trafficking of pleural mesothelial cells in idiopathic pulmonary fibrosis.

Abstract
Idiopathic pulmonary fibrosis (IPF) is characterised by myofibroblast proliferation leading to architectural destruction. Neither the origin nor the continued proliferation of myofibroblasts is well understood. Explanted human IPF lungs were stained by immunohistochemistry for calretinin, a marker of pleural mesothelial cells (PMCs). Chronic obstructive pulmonary disease (COPD) and cystic fibrosis (CF) lungs acted as controls. The number of PMCs per 100 nucleated cells and per photomicrograph was estimated along with the Ashcroft score of fibrosis. Mouse PMCs expressing green fluorescent protein (GFP) or labelled with nanoparticles were injected into the pleural space of mice given intranasal transforming growth factor (TGF)-β1. Mouse lungs were lavaged and examined for the presence of GFP, smooth muscle α-actin (α-SMA) and calretinin. Calretinin-positive PMCs were found throughout IPF lungs, but not in COPD or CF lungs. The number of PMCs correlated with the Ashcroft score. In mice, nanoparticle-laden PMCs were recoverable by bronchoalveolar lavage, depending on the TGF-β1 dose. Fluorescent staining showed α-SMA expression in GFP-expressing PMCs, with co-localisation of GFP and α-SMA. PMCs can traffic through the lung and show myofibroblast phenotypic markers. PMCs are present in IPF lungs, and their number correlates with IPF severity. Since IPF presumably begins subpleurally, PMCs could play a pathogenetic role via mesothelial-mesenchymal transition …

Pulmonary Hypertension secondary to Interstitial Lung Disease

Interstitial lung diseases (ILDs) may be complicated by the development of pulmonary hypertension (PH), which is associated with worse functional impairment and a poorer prognosis. This article reviews the current state of knowledge on the prevalence, pathogenesis, diagnosis and prognosis of ILD-related PH. Whether the treatment of ILD-related PH changes clinical outcomes is currently unknown, but the current studies are summarized and the authors’ perspective is offered. …

The Effects of Neuromuscular-Blocking Agents on Gas Exchange in Patients With Acute Respiratory Distress Syndrome

Abstract: The use of neuromuscular-blocking agents (NMBA) in ventilated patients with acute respiratory distress syndrome (ARDS) is controversial and largely empiric. Few trials looked at their effectiveness on gas exchange or in improving lung mechanics in patients with ARDS. Only one randomized, controlled trial compared the effects of NMBA on gas exchange in patients with ARDS receiving NMBA as compared with patients receiving placebo throughout a period of 48 hours. In this trial, the early use of NMBA in patients with ARDS was associated with a sustained improvement in oxygenation. The muscular paralysis induced by NMBA could reduce the consumption of oxygen linked to the work of breathing. Muscular paralysis could facilitate mechanical ventilation by preventing spontaneous breaths responsible for the dys-synchrony and worsening of gas exchange. Muscular paralysis could increase compliance of the thoracic wall and improve mechanical ventilation during ARDS. However, these hypotheses are controversial. Finally, preliminary data show that the muscular paralysis could provide better adaptation to mechanical ventilation and better satisfaction with the protective criteria for reduction of ventilator-associated lung injuries by homogenizing the distribution of tidal volume and positive end expiratory pressure. The role of new NMBA (benzylisoquinolines) in the occurrence of critical illness neuromyopathy is largely questioned in the recent literature. It is important to design new studies to explain the mechanisms of the improvement in oxygenation associated with NMBA and to evaluate whether the use of NMBA modifies the outcome of patients with ARDS. …

Exercise Prescription for Patients With Chronic Lung Disease

Chronic lung disease (CLD) and any consequent disease-related muscle myopathy along with deconditioning can cause both dyspnea and/or leg discomfort during exertion. These unpleasant experiences frequently lead an individual to reduce or even eliminate daily tasks which adversely impacts quality of life for the individual. The primary goal of exercise training is to restore the individual patient to the highest possible level of independent function. Improvements in exertional breathlessness observed following an exercise training program may be due to a physiologic training effect, enhanced mechanical efficiency, and/or psychologic desensitization. Any symptomatic patient with CLD who is motivated to participate should be referred to a pulmonary rehabilitation program. Exercise prescription is based on the principle of “overload” training. Although there is no optimal or best training regimen established for patients with CLD, we provide general guidelines for the mode, frequency, intensity, and duration of exercise training. The recommended minimal intensity of exercise training is 50% of peak work rate, although exercise at “maximal limits tolerated by symptoms” may also be prescribed. The recommended minimal duration of training is 20 to 30 minutes of continuous exertion. Resistance training should be incorporated into a comprehensive exercise program. One approach for patients with CLD to monitor their training intensity is to use a “dyspnea target” as a guide for intensity of training effort. …

Acquired Methemoglobinemia: A Case Report of Benzocaine-Induced Methemoglobinemia and a Review of the Literature

Benzocaine is widely used as a topical anesthetic and is also present in a number of over-the-counter preparations. Methemoglobinemia is a rare, but potentially serious, complication of its use; a fact that is not well documented in the Physician’s Desk Reference or product inserts. Unfamiliarity with this complication may delay diagnosis and appropriate therapy. A case of methemoglobinemia occurring as a complication of using benzocaine during bronchoscopy is presented and is followed by a review of the literature and discussion of the pathophysiology, clinical presentation, diagnosis, and treatment of acquired methemoglobinemia. Methemoglobin is incapable of carrying oxygen and is formed when the ferrous iron in the heme molecule is oxidized to the ferric state. The normal mechanisms that convert methemoglobin back to hemoglobin can be overwhelmed by many oxidant drugs, resulting in toxic methemoglobinemia. The diagnosis should be entertained when cyanosis, unresponsive to 100% oxygen therapy, appears suddenly, especially when exposure to an oxidant drug is established. Diagnosis is confirmed by multiple-wavelength cooximetry. Most cases require only decontamination and supportive care. Methylene blue is the specific antidote, but should be reserved for more severe cases or if comorbid conditions make mild hypoxia unadvisable. Exchange transfusion or hemodialysis may be indicated in patients who fail to respond to methylene blue. …