The Annals of Respiratory Medicine (AoRM), Vol II Issue 1

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

Andreas Hermes, Ulrich Gatzemeier and Martin Reck

Affiliation: Department of Thoracic Oncology, Grosshansdorf Hospital, Grosshansdorf, Germany

Correspondence: Andreas Hermes, Department of Thoracic Oncology, Grosshansdorf Hospital, Woehrendamm 80, 22927 Grosshansdorf, Germany. Tel: +49 4102 6010, Fax: +49 4102 601343, e-mail: pahermes@hotmail.com

ABSTRACT

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.

Influence of Atmospheric Parameters and Pollutants on Control of Breathing in Healthy Neonates

Sylvie Besson¹, Philipp Latzin^1,2, Georgette Stern¹, Marie-Pierre F. Strippoli², Claudia E. Kuehni², Martin Röösli² and Urs Frey³

Affiliations: ¹Department of Paediatric Pulmonology, Inselspital and University of Bern, Bern, Switzerland; ²Institute of Social and Preventive Medicine (ISPM), University of Bern, Bern, Switzerland and ³Universitäts-Kinderspital beider Basel (UKBB), Chair of Paediatrics, CMO, University Children’s Hospital Basel (UKBB), Postfach/ PO-Box, CH-4005 Basel, Switzerland

Correspondence: Urs Frey, PhD Ordinarius Päediatrie, ärztlicher Direktor, Universitäts-Kinderspital beider Basel (UKBB), Chair of Paediatrics, CMO, University Children’s Hospital Basel (UKBB), Postfach/ PO-Box CH-4005 Basel, Switzerland. Tel: +41 (0)61-685 62 56; Fax: +41 (0)61-685 60 01; e-mail: urs.frey@ukbb.ch

ABSTRACT

Exposure to air pollution increases the risk of Sudden Infant Death Syndrome and thus potentially influences control of breathing. This raises the question of whether tidal breathing parameters related to the control of breathing are influenced by atmospheric conditions and air pollution on the day of measurement (DOM).

In a prospective birth cohort study of 175 healthy term infants, we measured tidal breathing parameters including tidal volume, respiratory rate, minute ventilation, inspiratory time to total breath time (T _I/T _tot), ratio of time to peak tidal expiratory flow to expiratory time (T _PTEF/T _E), and peak tidal inspiratory flow at the age of 4-5 weeks. We assessed the association of these tidal breathing parameters with postnatal environmental tobacco smoke exposure (ETS), local atmospheric parameters, pollution levels of nitrogen dioxide (NO₂), ozone (O₃), and airborne particles with an aerodynamic diameter <10µm (PM₁₀) on the DOM using multiple linear regression analysis and adjusting for anthropometric data.

We found no consistent evidence of an association between atmospheric parameters, outside temperature and humidity, and tidal breathing parameters when adjusting for multiple testing. Anthropometric data (postconceptional age, length, and sex) were associated with control of breathing but not urban pollutant levels and ETS on the DOM.

Tidal breathing parameters, which are normally used to determine the maturational state of breathing control in infants, are influenced by anthropometric parameters. The acute effects of outside temperature and humidity, postnatal ETS, and outdoor air pollution levels on the DOM for the control of breathing were negligible in our study of healthy term infants.

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.

Early Detection of Lung Function Abnormalities in Young Children with Cystic Fibrosis

Catherine G Gangell¹ and Graham L Hall^1,2,3 On behalf of the Australian Respiratory Early Surveillance Team for Cystic Fibrosis (ARESTCF)^1,2,4,5

Affiliations: ¹Centre for Child Health Research, Telethon Institute of Child Health Research, University of Western Australia, Perth, Australia; ²Respiratory Medicine, Princess Margaret Hospital for Children, Perth, Australia; ³School of Paediatric and Child Health, University of Western Australia, Perth, Western Australia, Australia; ⁴Department of Respiratory Medicine, Royal Children’s Hospital, Melbourne, Australia and ⁵Murdoch Children’s Research Institute, Melbourne, Australia

Correspondence: Graham L Hall, Telethon Institute of Child Health Research, PO Box 855, West Perth, Western Australia 6872, Australia. Tel: +61 8 9489; Fax: +61 8 9489 7700; e-mail: grahamh@ichr.uwa.edu.au

ABSTRACT

The onset of lung disease in cystic fibrosis (CF) begins early in life with respiratory infection, inflammation, and structural lung damage all reported in infants with CF in the first months of life. As new treatments become available, it is essential that we have outcome measures that can be used to track disease progression and treatment efficacy. In this review, we have examined the role of lung function testing in infants and preschool children with CF. In particular, we have focused on the ability of the various lung function tests to detect the presence of respiratory pathogens and structural lung disease, increased inflammation, and the onset of acute exacerbations.

Impulse Oscillometry Testing in Chronic Cough in Children

Paraskevi Xepapadaki, IM Velissariou, DA Kafetzis, E Manoussakis, V Garis, P Saxoni-Papageorgiou and NG Papadopoulos

Affiliation: Allergy Department, 2nd Pediatric Clinic University of Athens, Athens, Greece

Correspondence: Paraskevi Xepapadaki, Allergy Department, 2nd Pediatric Clinic University of Athens, 13 Levadias Str., Goudi 11527, Greece. Tel: +30 210 7776964; Fax: +30 210 7776964; e-mail: panvik@hol.gr

ABSTRACT

INTRODUCTION

Chroni cough is a troublesome problem for children and the investigation to identify the underlying etiology is often inclusive.

OBJECTIVE

To assess lung function in children with chronic cough using impulse oscillometry (IOS).

METHODS

Sixty-seven children with chronic cough and 35 other children using age- and sex-matched controls were enrolled in this randomized control study. Patients and controls were subjected to IOS at the study entrance.

RESULTS

Airway resistance did not differ between cases and controls at baseline. Both cases and controls displayed significant reduction in resistance following bronchodilation; however, this was significantly more in cases (median ΔR5 Hz%: controls=−17.5, range: −45.1 to −8.7, cases=−6.4, range: −20.8 to −1.1, P<.001, median ΔR20 Hz%: controls=−11.5, range:−37.6 to −5.4, cases: −1.8, range:−20.1 to −0.4, P<.001, median ΔX5 Hz%: controls: −23.1, range: −48.6 to −9.9, cases: −8.6, range: −34.2 to −2.4, P=.01, median ΔZ5 Hz%: controls=−17.4, range: −44.8 to −9.8, cases: −6.8, range: −27.0 to −4.9, P<.001).

CONCLUSION

A proportion of patients with chronic cough tend to respond to bronchodilators by a significant reduction in airway resistance, as measured with IOS; an observation that supports an empirical trial of bronchodilators.

Spirometry and Respiratory Muscle Function During Ascent to Higher Altitudes

Sat Sharma and Bryce Brown

Affiliation: Section of Respirology, Department of Internal Medicine, University of Manitoba, St. Boniface General Hospital, Winnipeg, MB, Canada

Correspondence: Sat Sharma, Professor and Head Section of Respirology, Department of Internal Medicine, St. Boniface General Hospital, BG034, 409 Tache Avenue, Winnipeg, MB R2H 2A6, Canada. Tel: +1 204 237-2217; Fax: +1 204 231 1927; e-mail: ssharma@sbgh.mb.ca

ABSTRACT

Alterations in lung function at a high altitude (HA) influence exercise capacity, exacerbate hypoxia, and possibly promote predisposition to high-altitude illness. The effects of the HA on lung function and the mechanisms underlying these alterations are currently under investigation. Here, we present a review of the documented alterations in pulmonary physiology and lung functions at the HA in humans. As the first interface between the environment and the body, the lung plays a vital role in the transfer of oxygen from air to blood. The respiratory system adapts to hypoxic stress at rest and during exercise at a HA when oxygen and carbon dioxide flux from tissues is greater. Hypoxic stimuli induce an increase in ventilatory drive and metabolic cost incurred by the respiratory muscles in addition to substantial dyspnea, which may limit exercise tolerance. The exchange of oxygen and carbon dioxide is significantly affected owing to the lower driving pressure for oxygen from air to blood and more rapid transit time of blood across the pulmonary capillaries. Diffusion limitation and ventilation/perfusion mismatch additionally occur, thereby accentuating hypoxemia. Studies on lung and respiratory muscle functions have disclosed a fluctuating course for spirometric measurements, respiratory muscle strength, and endurance at the HA. Specifically, transient increases in these parameters initially occur on ascent to each new altitude, followed by a gradual decline during the longer stay. Despite these restrictions, humans cope remarkably well in times of considerable stress from the hypoxic environment.

Gastro-esophageal Reflux and Idiopathic Pulmonary Fibrosis—New Evidences of a Causal Relationship

Edoardo Savarino¹, Roberto Carbone², Elisa Marabotto¹, Simona Inferrera¹, Lorenzo Gemignani¹, Alberto Malesci³ and Vincenzo Savarino¹

Affiliations: ¹Division of Gastroenterology, Department of Internal Medicine, University of Genoa, Genoa, Italy; ²Division of Pneumology, Ospedale Regionale di Aosta, Aosta, Italy and ³Division of Gastroenterology, IRCCS Istituto Clinico Humanitas, Rozzano, Milan, Italy

Correspondence: Edoardo Savarino, Division of Gastroenterology, University of Genoa, Viale Benedetto XV n° 6, 16132 Genoa, Italy. Tel and Fax: +39 010 3538956; e-mail: edoardo.savarino@unige.it

ABSTRACT

Idiopathic pulmonary fibrosis (IPF) is a relentless and progressive lung disease of unknown etiology with no effective cure available. Recent data support the concept that chronic silent microaspiration (ie, aspiration of gastric acid, food, bile salts, and trypsin in forms of small droplets) could be involved in the pathogenesis, development, and progression of IPF. However, limited data are present on this direction and the precise relationship between chronic microaspiration and IPF remains poorly understood. It has been demonstrated that gastro-esophageal reflux (GER) plays an important role in causing extra-esophageal symptoms, including chronic bronchitis, bronchiectasis, diffuse panbronchiolitis, recurrent pneumonia, chronic cough, hoarseness, and asthma. Moreover, it is considered a presumed risk factor for microaspiration. Recent studies evidenced that it is strongly associated with IPF with an estimated prevalence of up to 90%. This review aims to explore the relationship between GER and pulmonary fibrosis by highlighting the pathophysiologic mechanisms, the role of diagnostic testing, as well as the therapeutic options for this important group of patients. Furthermore, the gaps in our current understanding of the diagnosis and treatment of chronic microaspiration in patients with IPF will be highlighted. Clarifying the role of chronic microaspiration in IPF is essential because it could potentially have a widespread clinical impact on the progression of this fatal disease.

The Role of Cigarette Smoking on Persistent Airflow Obstruction in Asthma

Neil C Thomson and Mark Spears

Affiliation: Respiratory Medicine, Institute of Infection, Immunity, & Inflammation, University of Glasgow, Glasgow, UK

Correspondence: Neil C Thomson, Respiratory Medicine, Institute of Infection, Immunity, & Inflammation, University of Glasgow & Gartnavel General Hospital, Glasgow G12 OYN, UK. Tel: +44 141 211 3241; Fax: +44 141 211 3464; e-mail: neil.thomson@glasgow.ac.uk

ABSTRACT

In developed countries approximately one-quarter of adults with asthma are active cigarette smokers. These individuals have poorly controlled symptoms, impaired therapeutic responses to corticosteroids, and increased rates of health care utilization compared to nonsmokers with asthma. Persistent airflow obstruction can develop in asthma, particularly in smokers. Accelerated loss of lung function in adulthood as well as genetic, environmental risk factors (other than smoking), and submaximal lung growth in childhood may also contribute to the development of persistent airflow obstruction in smokers with asthma. The best strategy for managing symptoms due to persistent airflow obstruction in smokers with asthma is uncertain and, in particular, which recommendations from international guidelines for asthma or COPD are most appropriate for the management of this patient group.

Cystic Fibrosis and Survival Beyond 40 Years

Nicholas J Simmonds

Affiliation: Department of Cystic Fibrosis, Royal Brompton Hospital, London, UK

Correspondence: Nicholas J Simmonds, Department of Cystic Fibrosis, Royal Brompton Hospital, London SW3 6NP, UK. Tel: + 44 (0) 20 73518041; Fax: + 44 (0) 20 73518052; e-mail: n.simmonds@imperial.ac.uk

ABSTRACT

Cystic fibrosis (CF) is the most common life-shortening, genetically inherited condition in the Caucasian population. Despite the lack of a cure for the underlying cellular defect, median survival continues to improve and is currently approximately 38 years—children born today with CF are predicted to live beyond 50 years of age. The demographics are changing with the number of affected adults beginning to outnumber children, and there is an increasing cohort of adults who have survived beyond 40 years of age. The current article provides a summary of the latest research on older CF patients. The aim was to characterize patients with CF who have lived beyond 40 years and discuss factors contributing to survival. Studies show that CF long-term survivors are a heterogeneous group; the majority has features suggestive of the classic disease but a significant proportion (the late diagnosis group) has a specific definable phenotype. Determinants of survival are complex but include maintaining good health in childhood and optimal BMI, FEV, FVC, and no Pseudomonas aeruginosa at the time of transition from pediatric to adult care. It is important to identify the factors contributing to extended life in this cohort of survivors, as we can use this information to improve care for the entire CF population.

The Importance of Distinguishing Mucinous and Nonmucinous Bronchioloalveolar Carcinomas

David Garfield¹ and Jacques Cadranel, MD-PhD²

Affiliations: ¹Associate Medical Director, ProMed Cancer Center, Shanghai, P. R. China and ²Service de Pneumologie et Réanimation - Hôpital Tenon, AP-HP and Université Pierre et Marie Curie Paris VI, Paris, France

Correspondence: David Garfield, Associate Medical Director, ProMed Cancer Center, #170 Danshui Road, LuWan District, Shanghai 200021, P.R. China. Tel: +86 21 5382 3936; e-mail: DavidGarfield@ProMedCancer.com

ABSTRACT

The bronchioloalveolar carcinomas (BAC) refer to peripheral lung adenocarcinomas characterized by their lepidic pattern of growth. They encompass a spectrum of tumors, including in situ adenocarcinomas, as well as minimally invasive and invasive adenocarcinomas but also having two different cytological subtypes: nonmucinous and mucinous. This spectrum of tumors shares certain characteristics: less smoking exposure, less male predominance, presentation as a solitary ground-glass/subsolid nodule/mass or multifocal air-space consolidation (or both), significantly fewer extrathoracic metastases, and a better prognosis than other adenocarcinomas. However, it has become increasingly evident that the nonmucinous and mucinous cytological subtypes are two separate diseases, mostly because of molecular characteristics as well as differing therapeutic results. This general review aims to clarify the new pathological classification, imaging, molecular biology, prognostic, and therapeutic features of BAC relating to their two different cytological subtypes.