Obesity causes lung dysfunction and breathing troubles by increased cysteinyl leukotrienes pathway

Increased body weight is a chronic health problem which has emanated from the globalized food market and dietary habit. This has led to the different types of ailments which occur in obese individual simultaneously and referred to as metabolic disorders. Metabolic syndrome includes conditions such as obesity, insulin-resistance, diabetes, hypertension, cardiovascular, and some forms of cancers. Lung dysfunction is also associated with increased body weight in which obese persons feel difficulty in breathing and could develop asthma like symptoms if not treated timely. Many studies have shown that such patients are difficult to treat with the regular asthma medicines, which suggests that probably breathing problem in obese people is caused by different mechanism and is different than allergic asthma. 

Elevated levels of cysteinyl leukotrienes (CysLTs) in the urine of obese asthma patients indicate elevated levels of biochemical pathway that forms this compound. CysLTs are responsible for the inflammation and swelling and can change the cell’s behavior by modifying their structure and function. In fact, LTs are known to cause lung problems in asthma and COPD in non-obese people and inhibitors of LTs receptors or of enzymes that make LTs are used as drug to treat such patients.

In the obese individual the fat deposits in the special cells called adipocytes which grows in number and size upon energy rich diet consumption. The adipocytes secret certain chemicals which attract macrophages, the policing cells in body which fight with pathogens and infectious agents and also some of the body’s own molecules and materials and removes them. In excessive accumulation of adipocytes, more macrophages get attracted to adipose tissue, get overactive and secrete molecules like cytokines, chemokines and also CysLTs which are released in blood and can cause inflammation in other body parts.

When it reaches to the lungs, CysLTs can activate the lung cells which can also secret the inflammation causing molecules and attract immune cells to the lungs. This scenario is similar to the early stage of development of asthma. Over the period of time these molecules can change the structure and function of lung cells including epithelial cells which can change into either mucous cells of fibrous cells and lung function may get severely affected. Mucous cells secret large amount of mucous which inhibit the gas exchange in the lung while fibrous cells affect the elasticity of the lung and lung cannot expand upon breathing.

How obesity causes these changes in the lungs is still not known and scientists are actively working to find answers. The mechanism once clear can help in treating such patients using the appropriate drugs.

Reference: Yadav UC, Srivastava SK. Cysteinyl Leukotrienes (CysLTs): Role in Obesity-Induced Asthma. Curr Mol Med. 2015; 15(7): 598-605.

  

Genetics of asthma

Asthma is the disease of airways, which include bronchi, bronchioles and alveoli in the lungs. Inflammation in these tube-like structures causes them to swell, secrete mucus, and clog the passages. It results in very low amount of air reaching to the lungs, causing breathlessness, chest tightness, difficulty in breathing and cough.

During the attacks, which can be caused by many reasons including allergens, pollution, sudden change in temperature, exercise, stress and many more, the tubes start constricting excessively blocking the flow of wind to the lungs.

It is not clear why some people are not affected by those same stimulants which cause asthma in others! The hereditary links have been suggested by many scientists. But, this suggestion can be questioned by the fact that many asthmatic children’s parents have never been diagnosed with asthma.

 Can this be due to the mutation in the genes acquired by parents, which latter on transmitted to the children?

The genetic link of asthma has been a point of debate for a long time now. Many genes have been identified which are suggest to be associated with the disease, but so far except for few, most of the associations have not been proved correct.

Children are the most affected from asthma as the disease, which first start with the allergic episodes and graduates to asthma attacks quickly. Some of those children get better with age and are able to manage their asthma with the modern and improved medicines and some changes in life style.

However a section of patients remain affected with the disease besides taking all those measures. They frequent to the hospitals, leaves from school and office, and also get affected by secondary infections of the lungs.

Scientists have been working to find reason for these differences. A new study has identified at least 15 mutations in the human gene that suggests link with childhood asthma. It is suggested that those patients whose asthma has genetic link are around 35% more likely to suffer from the disease as adult too.

The other indication of such association is that those with severe childhood asthma are more likely to have the disease as an adult.

Although at present it cannot be predicted with certainty which childhood asthma patients will be free from the disease and who will continue to have it as an adult, at most the new research on genetic link of asthma presents a hope that more focused studies will make our understanding better about the genetic association of this serious disease.