Pulmonology, Critical Care, Sleep Medicine

Lung Cancer in Never Smokers

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Lung cancer is the leading cause of death world wide. Tobacco smoking is the leading cause of deaths in patients of lung cancer. However according to several studies about 25% of lung cancer cases worldwide are not attributable to tobacco smoking. Non tobacco related lung cancer accounts for about 300,000 deaths annually worldwide. Thus, lung cancer in never smokers is the seventh leading cause of cancer deaths in  the world. It leads to more deaths world wide than pancreatic or prostate cancers. Although lung cancer in smokers is more common in males, lung cancer in never smokers occurs more frequently among women. In particular, there is a high proportion of never smokers in Asian women diagnosed with lung cancer.

Smoking-related carcinogens act on both proximal and distal airways inducing all the major forms of lung cancer while cancers arising in never smokers usually target  the distal airways. No clear-cut risk factor has emerged that can explain the relatively high incidence of lung cancer in never smokers, however multiple risk factors, including environmental, hormonal, genetic and viral factors, have been implicated in the pathogenesis of lung cancer in never smokers.  Environmental tobacco smoke (ETS) is a relatively weak carcinogen and can only account for a minority of lung cancers arising in never smokers.

There are four histological types of lung cancer and multiple minor or rare forms. For clinico-pathological reasons they are often divided into the broad categories of small cell lung cancer (SCLC) and non-small-cell lung cancer (NSCLC). NSCLCs are further divided into three major types, squamous cell carcinoma (SCC), adenocar-cinoma and large cell carcinomas. Large cell carcinomas represents  poorly or undifferentiated forms of the other types of cancers, it is a vaguely defined entity, and criteria for its diagnosis vary widely. No clear cut genetic predisposition has been elucidated for the lung cancer in never smokers. Molecular epidemiology studies, in particular of the TP53, KRAS and epidermal  growth factor receptor (EGFR) genes, demonstrate  different mutation  patterns .

As historically lung cancer is considered a disease of the smokers, the clinical threshold for investigating the symptomatic never smoker can be higher, thus delaying the diagnosis such that never smokers present at later stages of disease. In support of this assumption, two recent retrospective studies from the US and Singapore found that a higher proportion of never smokers presented with advanced-stage disease compared with smokers . Also another unforeseen bias could be the predominance of the disease in the female gender .

There are major clinical differences between lung cancers arising in never smokers and smokers and their response to targeted therapies. For example, a multivariate analysis of patients with stages I–IV adenocarcinoma of the lung identified never smoking as an independent predictor of improved survival (5-year survival 23% for never smokers and 16% for current smokers).

A large population-based analysis of 12,000 patients with NSCLC in southern California also reported significantly improved survival for never smokers (hazard ratio (HR) for death = 1.09 for current and former smokers versus never smokers) .The above-mentioned facts clearly suggest that lung cancer arising in never smokers is a disease distinct from the more common tobacco-associated forms of lung cancer.

Further efforts are needed to identify the major cause or causes of lung cancers arising in never smokers before successful strategies for prevention; early diagnosis and treatment therapies can be implemented.

Risk factor for lung cancers in non-smokers
Environmental tobacco smoke
Residential radon  
Cooking oil vapors  
Indoor coal and wood  
Viral factors: HPV 16/18  
Genetic Mutations

Salient Points
Lung cancer in never smokers is higher among women, particularly in Asia

Adenocarcinoma is the most frequent lung cancer subtype in never smokers

Some studies suggest that never smokers may present with advanced stage of lung cancer due to a higher clinical threshold for diagnosing lung cancer in non smokers.

Several studies have reported better survival for never smokers than smokers, independent of stage, treatment, co-morbidities and other known prognostic factors.

Note: Never smoker indicates persons with exposure to less than 100 cigarettes in a lifetime.

 

Asthma medication can modestly increase the risk of onset and progression of diabetes.

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Inhaled corticosteroid is an essential component of standard medication regimen for asthma. It is also used increasingly in COPD (Chronic Obstructive Pulmonary Disease). They reduce the airway inflammation and bring down the frequency of acute exacerbations of the above mentioned diseases. High doses on inhaled corticosteroids are used in the prevention and treatment of acute exacerbations of asthma and COPD. Previous research work has shown that the adverse effects of using high doses of inhaled corticosteroids include pneumonia, osteoporosis, cataracts and adrenal suppression.

In a new study published in the American Journal of Medicine, researchers affiliated with McGill University, Canada and Jewish General Hospital, Canada have claimed that use of inhaled corticosteroids especially in high doses modestly increases the risks of onset and progression of diabetes. Their report is based on the analysis of a large Quebec health insurance database from 1990 to 2005 which had patient details including the medications prescribed and diabetic status. Based on their calculations, the incidence rate of new diabetes in individuals using inhaled steroids was 14.2 per 1000 per year. Additionally 34% of known diabetics who were on oral hypoglycemic drugs were initiated on insulin indicating the disease progression. The study clearly shows that higher doses of inhaled corticosteroid of 1000mcg of fluticosone or equivalent increase the risk further.
 
It is well known that systemic steroid administration worsens the glycemic control. Though inhaled corticosteroids are presumed to act locally in the airway walls, when taken in high doses there is increased chance of it getting absorbed into the blood. This results in the usual systemic side effects of corticosteroids.  While inhaled corticosteroids are of proven benefit in asthma, its role in the management of COPD is controversial. Some doctors advocate the use of inhaled corticosteroids regularly for COPD and some have reservations about its utility. The authors opine that high doses of inhaled corticosteroids should be used only if the clinical condition warrants and only in diseases where it is of proven benefit.

Reference
Inhaled Corticosteroids and the Risks of Diabetes Onset and Progression. Samy Suissa, PhDab, Abbas Kezouh, PhDa, Pierre Ernst, MD, MScab
http://www.amjmed.com/article/S0002-9343(10)00648-0/abstract

 

Rinse your mouth after using inhaled asthma medications

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Individuals using inhalers regularly for asthma should rinse their mouth with water after administration of medications. One of the component of the combination inhalers is corticosteroid, which is very vital in reducing the airway inflammation and controlling asthma.But during inhalation some of these medications gets deposited in the oral cavity, throat and food pipe. This leads to the developement of fungal infection in these area over a long term. Fungal infections of mouth manifests as pain and difficulty on swallowing. Examination of the oral cavity may reveal  a thin white coat over the affected area.

If you are an asthmatic and if you have any of these symptoms, then you need to consult with your physician. Your doctor may prescribe a short course of antifungal medications.  

 

Temporarily increasing inhaled steroid dose may prevent asthma exacerbations.

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Summary
Quadrupling the dose of inhaled corticosteroid temporarily may prevent asthma exacerbations

Asthma affects an estimated 300 million people worldwide. The standard treatment regimen for asthma is a combination of inhaled beta agonist (bronchodilator) and inhaled corticosteroids (anti inflammatory). Asthmatics may suffer from acute exacerbations which manifests as breathlessness, wheezing and cough. These exacerbations increase health care utilization and general financial loss in the form of absenteeism from work etc. Some doctors suggest increasing the dose of inhaled corticosteroids two fold if the patients feel early symptoms of exacerbation. But two randomized trials didn’t show any advantage in doubling the inhaled steroid dose to prevent exacerbations.

In a study published in the American Journal of Respiratory and Critical Care Medicine, it has been reported that four fold increase in the dose of inhaled corticosteroids may reduce exacerbations and also the need for oral and intravenous corticosteroids if exacerbations occur. Acute exacerbations of asthma deteriorate health and wellbeing and results in increased health care utilization. The study suggests that increasing the inhaled steroid dose by four fold temporarily when the peak expiratory flow drops by 15% on two consecutive days or 30% drop in a single day may prevent acute exacerbation of asthma.

Larger studies need to be conducted to confirm this finding. Standard asthma management guidelines do not recommend increasing the dose of inhaled steroids temporarily when the asthma control deteriorates. The above is just for informational only. Kindly visit your physician in case of exacerbation of asthma.
 
Disclaimer: This article is based on a research work published in a standard journal. This is for information purposes only. Readers should not act based on information here without their physician’s consent.

For more information visit
http://ajrccm.atsjournals.org/cgi/content/short/180/7/598

Reference
Quadrupling the Dose of Inhaled Corticosteroid to Prevent Asthma Exacerbations: A Randomized, Double-blind, Placebo-controlled, Parallel-Group Clinical Trial; Janet Oborne, Kevin Mortimer, Richard B. Hubbard, Anne E. Tattersfield  and Tim W. Harrison

Last Updated on Sunday, 05 December 2010 12:38
 

Pneumonia – treatment by respiratory specialist leads to shorter hospital stay

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Summary:
Treatment by pulmonologist leads to shorter hospital stay in non-severe community acquired pneumonia.

Community acquired pneumonia is a frequent cause of hospital admissions worldwide. Pneumonia is treated by both respiratory medicine specialists (pulmonologist) and general physicians. In a retrospective review of hospital records at Nottingham city hospital revealed that early review by a respiratory physicians for non-severe community acquired pneumonia lead to shorter duration of hospitalization.
 
In the study publised in Thorax, the authors claim that respiratory physicians are more familiar with pneumonia severity assessment and treatment protocols resulting in more appropriate decision making. In addition their clinical experience with pneumonia is better resulting in greater confidence in discharging the patients earlier.

Last Updated on Saturday, 27 November 2010 22:21
 
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