The Annals of Respiratory Medicine

Mandating Influenza Vaccination of Health Care Workers: A Patient Safety, Quality of Care, and Public Trust Issue

Gregory A Poland^1,2,3, Robert M Jacobson^1,3, Jon Tilburt^2,4 and Sabine Wicker⁵

Affiliations: ¹Mayo Clinic Vaccine Research Group, Mayo Clinic College of Medicine, Rochester, MN, USA; ²Department of Internal Medicine, Mayo Clinic College of Medicine, Rochester, MN, USA; ³Department of Pediatric and Adolescent Medicine, Mayo Clinic College of Medicine, Rochester, MN, USA; ⁴Bioethics Research, Mayo Clinic College of Medicine, Rochester, MN, USA and ⁵Occupational Health Service, University Hospital-Frankfurt, Germany

Correspondence: Gregory A. Poland, MD, Mayo Vaccine Research Group, Mayo Clinic College of Medicine, 611C Guggenheim Building, 200 First Street SW, Rochester, MN 55905, USA. Tel: (507) 284-4968; Fax: (507) 266-4716; e-mail: poland.gregory@mayo.edu

ABSTRACT

Influenza causes yearly epidemic disease and occasional pandemics. Because of this, health care workers (HCWs) are routinely exposed to influenza in the course of their patient care duties. As a result, transmission from HCW to HCW, and HCW to patients occurs, leading to evidence for increased morbidity and mortality among the patients cared for by unimmunized HCWs. Despite the existence of safe and effective influenza vaccines, the majority of HCWs still fail to receive seasonal influenza vaccines. Thus, influenza immunization of HCWs must be seen as a patient safety and quality of care issue. The failure to be immunized, we believe, represents a failure of ethical medical and nursing practice, a failure of leadership among hospitals and health care institutions, and a breach of the public trust accorded to the healing professions. Herein we discuss the rationale and evidence for requiring influenza immunization of HCWs; describe the current state of such programs in the United States and Europe; discuss the implementation of mandatory programs and their results at the practice, institutional, legislative, and professional society levels; and conclude with a call for mandating influenza immunization of all HCWs.

Etiological Factors in COPD Exacerbations

Exacerbations of chronic obstructive pulmonary disease (COPD) are associated with increased systemic and airway inflammation and are a major cause of morbidity, mortality, and hospital admission. Exacerbations may be triggered by environmental factors but the majority are infectious in etiology. Bacteria are detected in around 50% of exacerbations and increases in bacterial load and species strain changes are potential key causative mechanisms in acute exacerbations of COPD. Polymerase chain reaction techniques have established that, in half to two-thirds of exacerbations, viruses may be causative pathogens with rhinovirus the most frequently detected respiratory virus at exacerbation. COPD patients may be more susceptible to respiratory virus infections and further work is required to explore the interactions between viral and bacterial infections at exacerbation. Future studies may target the frequent exacerbator phenotype and those patients colonized with potentially pathogenic microorganisms for long-term antibiotic therapy. Respiratory viral infections are also an important therapeutic target for COPD as prevention of viral infection may reduce exacerbation frequency and, hence, improve health status.

New Views on Relaxin and Relaxin-Receptor Agonists for the Treatment of Lung Fibrosis: Evidences From In Vivo Models

INTRODUCTION

Fibrosis is a pathophysiological response to injury characterized by excess, abnormal extracellular matrix (ECM) deposition disrupting the normal tissue architecture and function of affected organs. Lung fibrosis may occur as a component of systemic or local diseases, but the most pernicious clinical form is idiopathic pulmonary fibrosis (IPF), which represents a major challenge for pneumologists, being refractory to any conventional therapy. This has prompted the development of suitable animal models of lung fibrosis to test novel therapies.

OBJECTIVES

This mini-review summarizes the current knowledge on the antifibrotic properties of relaxin, a natural hormone capable of modulating ECM turnover in multiple target organs, which can be viewed as a promising antifibrotic drug. In fact, human recombinant relaxin has been and is currently being investigated in clinical trials due to its favorable bioactivity profile.

RESULTS AND CONCLUSION

Based on several in vitro and in vivo studies, relaxin has emerged as a key endogenous factor involved in the regulation of ECM synthesis and remodeling by fibroblasts. Knockout mice for relaxin or its receptor are prone to heart, kidney, and lung fibrosis: in the former animal model, the profibrotic trend can be reverted by exogenous administration of the hormone, implicating its therapeutic potential. To overcome the intrinsic limitations of the peptide properties of the hormone, low molecular weight relaxin receptor agonists have been synthesized and are currently being evaluated as alternative treatments. As shown using a mouse model of bleomycin-induced lung fibrosis, these compounds are capable of blunting the pulmonary inflammatory reaction to bleomycin and the subsequent enhanced collagen deposition. Taken together, these existing notions and clues suggest that relaxin and related molecules deserve to be further investigated as possible antifibrotic drugs.

Pulmonary Hypertension in Idiopathic Pulmonary Fibrosis

Idiopathic pulmonary fibrosis (IPF) is a progressive fibrotic lung disease with a poor outcome. Recently, there has been a growing appreciation for the presence of secondary pulmonary hypertension in patients with IPF (IPF-PH), and research has begun in earnest to understand the effects of PH on the clinical course and outcome of patients with IPF. The pathogenesis of IPF-PH is unclear but may be related to intermittent hypoxia, loss of vascular density within the fibrotic parenchyma, vascular remodeling, or endothelial dysfunction. Elevated pulmonary pressures, confirmed by right heart catheterization (RHC), affects nearly one-half of IPF patients undergoing evaluation for lung transplantation candidacy. Doppler echocardiography (TTE) is a noninvasive and relatively inexpensive way to screen for IPF-PH, but it is notoriously inaccurate: nearly 50% of IPF patients have a greater than 10mmHg difference between TTE and RHC estimates. Other non-invasive markers of PH in IPF patients are imperfect as well, and there is little correlation between IPF severity and the presence of PH. The presence of PH significantly worsens prognosis in patients with IPF: nearly one-third of patients with IPF-PH die within one year of being diagnosed with PH. Although there are currently no proven effective therapies for IPF-PH, well-designed trials are underway. Additional research is needed to more clearly define the epidemiology and risk factors for IPF-PH and to identify effective treatments.

Childhood Tb: Global Epidemiology and Impact of HIV

Tuberculosis (TB) is still one of the deadliest infectious diseases in the world killing nearly two million people every year, mostly in developing countries where the prevalence is closely linked to poverty and malnutrition. Tuberculosis continues to be an important cause of morbidity and mortality among children worldwide, contributing 10–15% of all incident cases. Challenges in estimating the burden of childhood TB include the difficulty in establishing a definitive diagnosis, the higher prevalence of extrapulmonary disease (compared to adults), and the lower public health priority it has received. In high human immunodeficiency virus (HIV) prevalent settings, children (both infected and affected) are at high risk of TB infection due to close proximity with young adults who are most likely to be HIV-infected and in whom TB is the commonest opportunistic infection. Further, due to the high prevalence of other opportunistic infections among HIV-infected children and the lack of a gold standard, diagnosis of TB is often a challenge in this population. Bacilli Calmette-Guérin (BCG), despite its variable efficacy in different populations, is still the most widely used preventive measure against TB, but has safety concerns in HIV-infected infants. In the long-term, the burden of childhood TB can be reduced by effectively diagnosing and treating all infectious TB patients in the community, within a strong control program. In the meantime, more attention needs to be given to contact tracing and screening of household contacts of adult infectious patients, with provision of preventive therapy to all eligible children. Treatment of children with latent TB infection would also serve to reduce the pool of individuals from which future TB could arise. Additional efforts are needed to test and validate new diagnostic tools and strengthen surveillance systems for more reliable data on TB in children.

Efficacy of Second and Subsequent Lines of Chemotherapy in Patients with Small Cell Lung Cancer-a Retrospective Single Institution Analysis

PURPOSE

The aim of this retrospective study is to present data on efficacy and toxicity of second and subsequent lines of chemotherapy in an unselected contemporary patient population with small cell lung cancer (SCLC) in limited disease (LD) and extensive disease (ED) stage.

PATIENTS AND METHODS

From June 2004 to June 2008, our electronic database including all in-patient and out-patient contacts was searched for patients with newly diagnosed SCLC. We identified 397 cases. Data were collected on patient characteristics, chemotherapy, side effects, response on treatment and survival. Time to progression (TTP) was assessed for every line of chemotherapy.

RESULTS

155 patients had LD SCLC. Response rate (RR) reached 76%. Thoracic radiation therapy was administered in 72%, Prophylactic cranial irradiation in 33%. TTP was 7.5 months. 51% received 2nd line treatment. In two thirds of these cases, the primary regimen was given as re-induction therapy. TTP in this group was 11.5 months, RR 36% and median survival 30 months. In patients with true second line therapy, RR was 8% and median survival median reached only 16 months.

CONCLUSION

Second line treatment should be given to all patients with recurrent SCLC in good performance status. Third line therapy is reasonable in patients with good PS and sensitive tumor on first line therapy.

The Value of Pulmonary Function Testing in Bone Marrow Transplantation

INTRODUCTION

The pre- and postbone marrow transplant pulmonary functions testing are widely used as standard clinical practice. However, whether there is sufficient reliable data to support and validate this practice is not confirmed.

OBJECTIVE

In this article we will review the publications that have assessed the role of pretransplant pulmonary functions tests for bone marrow transplant patients in identifying those patients who are at high risk for developing posttransplant noninfectious pulmonary complications.

METHODS

PubMed search to identify the publications that have investigated the role of pretransplant pulmonary functions tests in predicting posttransplant pulmonary complication in patients undergoing bone marrow transplant.

RESULTS

Several small studies suggest a risk of posttransplant complications associated with pretransplant obstructive patterns.

CONCLUSION

Large randomized control trials examining pretransplant lung function are needed, including both nonmyeloablative and myeloablative conditioning regimens, to determine how pretransplant pulmonary function data can be applied clinically to reduce patient risk for significant pulmonary complications and mortality.

Pulmonary MALT Lymphoma: Clinical, Molecular, and Therapeutic Aspects

REVIEW ARTICLE


Marie Wislez^1, Raphaël Borie^2, Catherine Thieblemont^3, Marie-France Carette^4, Martine Antoine⁵ and Jacques Cadranel¹

Affiliations: ¹Service de Pneumologie et Réanimation, Centre de Compétence des Maladies Rares Pulmonaires, Hôpital Tenon, AP-HP, Faculté de Médecine Pierre et Marie Curie, Université Paris VI, Paris, France; ²Service de Pneumologie, Hôpital Bichat, AP-HP, Université Diderot-Paris VII, Paris, France; ³Service d'Hémato-Oncologie, Hôpital Saint-Louis, AP-HP, Université Diderot-Paris VII, Paris, France; ⁴Service de Radiologie, Hôpital Tenon, AP-HP, Faculté de Médecine Pierre et Marie Curie, Université Paris VI, Paris, France and ⁵Service d'Anatomie Pathologique, Hôpital Tenon, AP-HP, Faculté de Médecine Pierre et Marie Curie, Université Paris VI, Paris, France

ABSTRACT

This general review aims to clarify the pathophysiological, diagnostic, prognostic, and therapeutic features of mucosa-associated lymphoid tissue (MALT) lymphoma.

MALT lymphoma is the most common type of pulmonary lymphoma. It develops in MALT and, in most cases, it is slow-growing and presents as an asymptomatic chronic alveolar opacity visible on radiography. The prognosis of the disease is excellent, and the current treatments available are discussed in this review (decision not to treat, surgery, single-agent chemotherapy).

Keywords: primary pulmonary lymphoma (PPL), mucosa-associated lymphoid tissue (MALT), chronic alveolar opacity.

Correspondence: Jacques Cadranel, Service de Pneumologie et Réanimation, Hôpital Tenon, 4 rue de la Chine 75970, Paris Cedex 20, France. Tel: +33 1 56 01 65 31; e-mail: jacques.cadranel@tnn.aphp.fr

Chemotherapy of Malignant Pleural Mesothelioma: Where Are We Now and Where Are We Going?

REVIEW ARTICLE


Gunnar Hillerdal

Affiliation: Department of Lung Medicine, Karolinska University Hospital, Stockholm, Sweden

ABSTRACT

The incidence of malignant pleural mesothelioma is increasing in most industrialized countries and even more so (though from low numbers) in developing countries. The prognosis is poor, but the median survival time has improved with modern chemotherapy, and some patients can live many years in good shape. The combination of pemetrexed and a platin compound is now the standard treatment all over the world with many studies confirming its efficiency. Unfortunately, there are no other drugs or combinations of drugs that have been compared to the standard treatment. Studies on such combinations are usually small, and even if they seem to have given positive results this could be due to the selection of patients. However, lacking alternatives they can be tried as second-line or when pemetrexed is contraindicated. These drugs include Vinorelbine, liposomized Doxorubicin, Gemcitabine, and others in various combinations. It is not possible to directly compare different studies, because the selection of patients varies too much. Many second-line studies are on-going and should be encouraged, and hopefully new active drugs can be found this way. Biological therapies have so far been a disappointment with this tumor, and in vitro effects can rarely be verified in clinical studies. Exceptions are a few promising studies with histone deacetylase inhibitors that are on-going. With the present very active research, more effective treatment options of malignant mesothelioma are likely in the future.

Keywords: malignant pleural mesothelioma, chemotherapy, review

Correspondence: Gunnar Hillerdal, Department of Lung Medicine, Karolinska University Hospital, 171 76 Stockholm, Sweden. Tel: +46-8-5177000; Fax: +46-8-332998; e-mail: gunnar.hillerdal@karolinska.se

An Update on Bronchodilator Treatment of Chronic Obstructive Pulmonary Disease (COPD)

REVIEW ARTICLE


Walter Vincken

Affiliation: Respiratory Division, University Hospital Brussels (UZ Brussel), University of Brussels (Vrije Universiteit Brussel), Belgium

ABSTRACT

Although the main characteristic of chronic obstructive pulmonary disease (COPD) is relentlessly worsening airflow limitation, many patients show some degree of reversibility and, more importantly, clinically relevant improvements in dyspnea, exercise capacity, and health status following the administration of a bronchodilator. The mechanism through which bronchodilators effect these improvements appears to be a reduction in hyperinflation both at rest and during exercise. Bronchodilators also consistently reduce exacerbations. As a result, bronchodilators have become the recommended cornerstone of maintenance treatment of COPD.

Three classes of bronchodilators are currently available: the oral methylxanthine theophylline, both short-acting (SA) and long-acting (LA) inhaled ß2-adrenergic receptor agonists (BA), and anticholinergics (AC) or muscarinic receptor antagonists (MA). The SA inhaled bronchodilators are still used for rescue treatment, but should, for maintenance treatment, be replaced by their LA counterparts for reasons of both efficacy and convenience. Evidence also advocates the introduction of LA inhaled bronchodilators early in the disease process. Among the available LA inhaled bronchodilators, the once daily LAMA tiotropium appears a safe, effective, and convenient choice to initiate maintenance treatment with, but the advent of equally effective and convenient once daily LABAs and LAMAs may offer clinicians a valid alternative. Furthering the debate as to which bronchodilator to start maintenance treatment with is somewhat superfluous, as the constant finding that a combination of bronchodilators acting through different mechanisms has at numerous times been shown to be superior and perhaps safer than treatments with a single bronchodilator class. Once-daily combinations of LAMA and LABA formulated into one single device are now under way and probably will become the preferred maintenance treatment for COPD patients. Finally, another important step forward in the treatment of COPD will be the development of inhalation devices delivering aerosols with optimal pulmonary deposition and equipped with features that facilitate their correct handling by the COPD patient.

Keywords: COPD, treatment, bronchodilators, inhalation

Correspondence: Walter Vincken, Respiratory Division, University Hospital Brussels (UZ Brussel), 101 Laarbeeklaan, 1090 Brussels, Belgium. Tel: +32 (0)2 4776841; Fax: +32 (0)2 4776840; E-mail: walter.vincken@uzbrussel.be

Pulmonary Arterial Pressure during Rest and Exercise (from Geneva, 1961 to Dana Point, 2008)

REVIEW ARTICLE

Gabor Kovacs and Horst Olschewski

Affiliation: Medical University of Graz, Division of Pulmonology, Graz, Austria


ABSTRACT

The first hemodynamic definition of pulmonary hypertension was introduced at a World Health Organization (WHO) meeting on Primary Pulmonary Hypertension in Geneva in 1973. Pulmonary hypertension was defined as mean pulmonary arterial pressure (mPAP) >25 mmHg at rest or >30 mmHg during exercise. This hemodynamic definition was broadly used by clinicians and researchers, and was adopted at upcoming world conferences in Evian 1998 and Venice 2003. At the last world conference in Dana Point in 2008, however, the hemodynamic definition was discussed again. According to the published literature, based on invasive measurements in healthy individuals, resting mPAP is 14.0±3.3 mmHg, is virtually independent of gender and geographical origin, and is only mildly influenced by posture and age. During exercise, however, mPAP is dependent on exercise level and age. The Dana Point statement defines the normal range of resting mPAP between 8 and 20 mmHg and pulmonary hypertension as resting mPAP >25 mmHg. As it may not be possible to define a single upper limit of normal mPAP fitting to all individuals and all exercise levels, the exercise part of the old definition of pulmonary hypertension was abandoned. Further studies are warranted to better determine the natural history of patients with mPAP between 20 and 25 mmHg and an out-of-proportion increase in mPAP during exercise.

Keywords: pulmonary hypertension, pulmonary arterial pressure, exercise, hemodynamic definition, normal

Correspondence: Gabor Kovacs, Medical University of Graz, Division of Pulmonology, Auenbruggerplatz 20, 8036 Graz, Austria. e-mail: gabor.kovacs@klinikum-graz.at

Talc Particle Size: Does it Influence the Acute Systemic Inflammatory Response in Talc Pleurodesis?

REVIEW ARTICLE


Eduardo H. Genofre, Francisco S. Vargas and Evaldo Marchi

Affiliation: Laboratory of Pleura Pulmonary Division, Heart Institute (InCor), University of São Paulo Medical School, São Paulo, Brazil


ABSTRACT

Talc has been the most used agent worldwide for induction of pleurodesis. However, despite its popularity, wide availability, low cost, and high success rate, there is great concern about the adverse effects of intrapleural talc application. Among these, we highlight acute respiratory failure that can be potentially fatal. The mechanism by which talc pleurodesis produces local and systemic inflammatory response is not well known. It is speculated that the large variation in particle size and the presence of contaminants in talc composition may be responsible for the effects observed in clinical practice. Experimental studies have shown that talc of smaller particles (<5 µm) may migrate to several organs. In addition, the intense local inflammation induced by talc may promote the loss of integrity of the capillary barrier, allowing the free flow of inflammatory mediators between the pleural and the systemic compartments. Despite the proven efficacy of talc in producing pleurodesis, its safety is not absolute.

Keywords: Pleura, pleural effusion, pleurodesis, magnesium silicates, inflammation, inflammation mediators, talc

Correspondence: Eduardo Henrique Genofre, MD, PhD; Av. Lins de Vasconcelos, 1455–Ap 141–Bl 01–CEP 01537-001–Sao Paulo–SP–Brazil. e-mail: ehgenofre@uol.com.br; ehgenofre@me.com

Gender Differences in COPD Mortality: A Descriptive Review of the Literature

REVIEW ARTICLE

Juan P de Torres^1, Ciro Casanova² and Bartolome R Celli³

Affiliations: ¹Pulmonary Department, Clinica Universidad de Navarra, Pamplona, Spain; ²Pulmonary Department, Hospital Ntra Sra de Candelaria, Tenerife, Spain; and ³Pulmonary Department, Brigham and Women Hospital, Harvard Medical School, Boston, Massachusetts, USA


ABSTRACT

Chronic obstructive pulmonary disease (COPD) will be one of the leading causes of death in the near future. Traditionally a disease associated with the male gender; in the last decades COPD has become an increasing problem among women. In the United States as well in other developed countries like Canada, the United Kingdom, and Finland, the number of cases, hospitalizations, and deaths among women have exceeded those among men. Little is known about gender differences in mortality in COPD patients. Lately, a few studies have challenged the knowledge that women with the disease have a better survival than men. This article intends to review, from a gender perspective, factors affecting COPD survival and the existing literature about gender differences in mortality.

Keywords: gender, COPD, mortality

Correspondence: Juan Pablo de Torres, Pulmonary Department, Clinica Universidad de Navarra, Av Pío XII, 36 CP 31008, Pamplona, Spain. Tel: 0034 948255400; Fax: 0034 296500; e-mail: jupa65@hotmail.com

Inhaled Corticosteroids and Lung Cancer Chemoprevention in Chronic Obstructive Pulmonary Disease Patients: What Should We Make of What We Observe?

Review Article


A Victor Kiri

Affiliation: Department of Peri Approval Clinical Excellence, PAREXEL International, Uxbridge, UK


ABSTRACT

Chronic obstructive pulmonary disease (COPD) is a major cause of mortality and morbidity worldwide with an estimated 2.75 million deaths in 2000 (fourth leading cause of death). The lung is a major site of cancer in the world today, representing about 13% of all new cancers. Epidemiological data indicate that COPD patients are at increased risk of cancer, especially lung cancer, and COPD is recognized as a major risk factor for lung cancer independent of the effect of smoking. Both diseases incur significant healthcare and societal costs, and smoking cessation remains the most effective control for reducing the risk of developing either disease. Although no randomized controlled trial has demonstrated an effective therapy against COPD mortality, many trials have reported positive results for inhaled corticosteroids (ICS) and long‐acting bronchodilators (LABA) on lung function improvement, reduction in exacerbation, and reduction in health‐related costs. Indeed, observational studies have suggested some COPD survival benefits from the combined use of both ICS and LABA and, more notably, a few others have also found evidence of reduction in lung cancer risk among COPD patients exposed to ICS. The possibility that ICS may possess such chemopreventive effects in COPD deserves better attention.

Keywords: chronic obstructive pulmonary disease (COPD), lung cancer, chemoprevention, inhaled corticosteroids, peripheral adenocarcinoma, squamous cell carcinoma
Correspondence: Victor A Kiri, Department of Peri Approval Clinical Excellence, PAREXEL International, Uxbridge, Middlesex UB8 1LZ, UK. Tel: (44)‐1895–614760; Fax: (44)‐1895–614277; e‐mail: Victor.Kiri@PAREXEL.com

The Relation between Right‐to‐Left Shunt and Migraine: Focus on Pulmonary Arteriovenous Malformations

Review Article


WF Marco van Gent¹, HAM Michiel van Helden¹, J Johannes Mager² and C Martijn Post¹

Affiliations: Department of ¹Cardiology and ²Pulmonology, St Antonius Hospital, Nieuwegein, the Netherlands


ABSTRACT

Migraine is a common and disabling disorder. Pulmonary arteriovenous malformations (PAVMs) cause a right‐to‐left shunt (RLS). An increased prevalence of migraine, particularly migraine with aura (MA+), has been shown in patients with a RLS of both pulmonary and cardiac origin. The prevalence of PAVM in patients with hereditary hemorrhagic telangiectasia (HHT) is 15–45%. Therefore, the HHT population provides a unique opportunity to study the RLS–migraine hypothesis. Embolization of PAVMs might reduce the prevalence of migraine, and an association between PAVM in HHT patients and MA+ was shown recently in a prospective study. The current review focuses on the evidence of a real association between an intrapulmonary RLS and migraine, and summarizes the possible underlying pathogenesis.

Keywords: pulmonary arteriovenous malformations, right‐to‐left shunt, migraine, hereditary hemorrhagic telangiectasia, patent foramen ovale
Correspondence: M C Post, Department of Cardiology, St Antonius Hospital, Koekoekslaan 1, 3435 CM Nieuwegein, the Netherlands. Tel: (31)‐30‐6099111; Fax: (31)‐30‐6092274; e‐mail: m.post@ antoniusziekenhuis.nl

Assessment of Interstitial Lung Disease in Systemic Sclerosis and Impact on Disease Progression and Outcomes

Review Article


E Koumakis , A Kahan  and Y Allanore

Affiliation: Paris Descartes University, Rheumatology A Department, Cochin Hospital, APHP, 75014 Paris, France


ABSTRACT

Interstitial lung disease (ILD) has emerged as a major cause of mortality in systemic sclerosis (SSc), representing about 30% of SSc‐related deaths. ILD occurs in up to 75% of patients with SSc, but progresses to severe restrictive lung disease in only about 10–15% of these patients. Histopathologic lesions are characterized in most cases by non‐specific interstitial pneumonia. Risk factors for the occurrence of pulmonary fibrosis include diffuse cutaneous SSc and anti‐topoisomerase I antibodies. ILD often remains asymptomatic, and the presence of symptoms often indicates advanced lung disease. Therefore, early detection of ILD is a major concern in SSc patients. The diagnosis and follow‐up of SSc‐related ILD (SSc‐ILD) is based essentially upon non‐invasive examinations including pulmonary function tests and high‐resolution pulmonary computed tomography scan (HRCT). The utility of outcome measures for pulmonary involvement in SSc has been assessed by the OMERACT filter, according to several criteria (truth, discrimination, and feasibility). Risk factors for the deterioration of lung function include low baseline forced vital capacity (FVC) and diffusing capacity of the lungs for carbon monoxide (DLCO) values, and initial HRCT abnormalities. This article details and summarizes the available data on prognostic factors for SSc‐ILD and the association of lung involvement with disease progression in SSc.

Keywords: systemic sclerosis, interstitial lung disease, pulmonary function tests, computer tomography (CT) scan
Correspondence: Yannick Allanore, Service de Rhumatologie A, Hôpital Cochin, Université Paris Descartes, 27 rue du Faubourg Saint‐Jacques, 75014 Paris, France. Tel: (33)‐1‐58‐41‐25‐72; Fax: (33)‐1‐58‐41‐26‐24; e‐mail: yannick.allanore@cch.aphp.fr

Role of Leukotriene B4 Receptor Antagonist in Pulmonary Fibrosis

Review article


Takehiro Izumo, Mitsuko Kondo, Naoki Arai and Atsushi Nagai

Affiliation: First Department of Medicine, Tokyo Women’s Medical University School of Medicine, Shinjuku-ku, Tokyo, Japan


ABSTRACT

Leukotrienes (LTs) are important chemoattractants for leukocytes and play a pivotal role in the pathogenesis of inflammatory and immune disease, and recent evidence suggests that LTs also play an important role in pulmonary fibrosis. The synthesis of leukotriene B4 (LTB4) and cysteinyl leukotriene (cysLT) is catalyzed by 5‐lipoxygenase. Elevated levels of LTB4 in bronchial alveolar lavage fluid have been reported in allergic diseases and pulmonary fibrosis. Recent reports using LTB4 receptor (BLTR) antagonists have revealed that ligation of BLTR by LTB4 is important for the activation and recruitment of inflammatory cells including neutrophils, eosinophils, monocyte/macrophages, and T cells to inflamed tissues in inflammatory diseases. Although it is about 30 years since LTB4 was discovered in 1979, recent research about BLTR antagonists has revealed the important roles of the LTB4/BLTR pathway in the pathophysiology of pulmonary diseases, such as bronchial asthma and pulmonary fibrosis. We reported recently that BLTR antagonists inhibited the development of bleomycin‐induced pulmonary fibrosis in mice by decreasing the inflammation and altering transforming growth factor β, interleukin (IL)‐6, IL‐13, and interferon γ. Current therapy for pulmonary fibrosis is ineffective, and the disease has a poor outcome and is associated with severe morbidity. Corticosteroid therapy for pulmonary fibrosis is not effective and does not prevent progression. Targeting of the LTB4/BLTR pathway may be an important strategy in the treatment of pulmonary fibrosis.

Keywords: pulmonary fibrosis, leukotriene B4, leukotriene B4 receptor (BLTR), leukotriene B4 receptor antagonist, cysteinyl leukotriene
Correspondence: Takehiro Izumo, First Department of Medicine, Tokyo Women’s Medical University, School of Medicine, 8‐1 Kawada‐cho, Shinjuku‐ku, Tokyo, 162‐8666, Japan. Tel: (81)‐3‐3353‐8111; Fax: (81)‐3‐5379‐5457; e‐mail: drtake@s6.dion.ne.jp