Unraveling the role of HIF and epigenetic regulation in pulmonary arterial hypertension: implications for clinical research and its therapeutic approach



hypoxic pulmonary hypertension :: Article Creator

IPF: Death Knell For The Lungs?

From common cold, flu, high blood pressure, blood clots in the lungs, lung cancer to as severe as Idiopathic pulmonary fibrosis (IPF) disease that claimed the late tabla maestro Ustad Zakir Hussain's life, all are currently in focus. Reputed pulmonologists Dr. D.P. Bansal and Dr. Sulaiman Ladhani weigh in.

Breathe easy and healthy. That is what doctors recommend for eight to 80. But inhaling fresh air from clean surroundings seems scarce nowadays. With the surge in SPM count (suspended particulate matter) and a blanket of smog covering every urban space this winter, human lungs are being badly hit. Even the demand for air-purifiers in most homes this season is noticing a huge spike. As a result, lung diseases and associated complications are on the rise. The current talking point is IPF or the chronic idiopathic pulmonary fibrosis ailment that caused ace internationally-acclaimed musician Hussain's demise.

Idea About IPF

IPF is an acute long-term lung disorder that damages the tissue encircling the air sacs or alveoli in the lungs.

Consequently, the lung tissue thickens and stiffens and can eventually scar the lungs with permanent effect, which is called fibrosis.

"Due to this developed condition, a patient may gradually find it difficult to breathe in and out. It is a rare, progressive impairment of the respiratory system, characterised by the hardening of lung tissue and an irreparable deterioration in lung function. Such cases can be detected through certain findings from CT Scan and lung biopsy," informs Dr. D.P. Bansal, medical director and consultant at pulmonary and critical care medicine unit of Olive Hospitals in Hyderabad.

Transplant

It is often enquired if a lung transplant is possible in critical cases or is there a life threat? "Lung transplant is an option for end-stage IPF with no other alternative left to resort to," confirms Dr. Bansal.

In Case of comorbidity

One also wonders if IPF can worsen the co-existing conditions of a patient with heart disease, high blood pressure, bronchial asthma and diabetes. "IPF can cause the right heart failure due to low oxygen levels," states Dr. Bansal.

Perils

IPF is reported to intensify the risks of high blood pressure in the lungs, heart attack, stroke, blood clots in the lungs, lung cancer and lung infections.

"IPF can cause pulmonary hypertension due to hypoxic vasoconstriction (a physiological response happening at the time when lungs are exposed to low oxygen levels or hypoxia. This is good for a brief period as it helps redirect blood flow to the better-ventilated or oxygenated areas of the lungs) of pulmonary vasculature (a specialised network of vessels that connects the lungs and the heart. Its chief function is to exchange gases, removing carbon dioxide and adding oxygen to the blood) inducing the right heart failure. Also, chronic scarring of the lungs due to IPF can be a risk factor for lung cancer," reports Dr. Bansal.

Although its precise root cause is yet unknown but risk factors, such as smoking, air pollution and genetic predisposition may contribute to IPF's development. "Early diagnosis through tests like CT scans, pulmonary function tests and biopsies is crucial as symptoms often mimic other kinds of respiratory problems," suggests Dr. Ladhani.

Treatment

Specific medications used in treating IPF are, namely nintedanib and pirfenidone, among others. "These drugs appear to decelerate disease aggravation. Sad but true, the disease is not curable," rues Dr. Bansal.

"However, the supportive care provided to mitigate the crisis includes oxygen therapy, smoking cessation and vaccination against pneumonia/flu," he assures.

Echoing his opinion, Dr. Ladhani says: "Since there is no remedy and recovery, treatments like anti-fibrotic medications, pulmonary rehabilitation, oxygen therapy and in some grave cases, lung transplants can help manage the disease and improve a suffering patient's quality of life. Lifestyle changes, mental health support and early medical intervention are key to slowing down the advancement of IPF and promoting a stable condition.

Hereditary

Most cases of IPF are erratic in nature. Cases like familial pulmonary fibrosis (FPF) are described as a lung disease that affects minimum two members of the same biological family and it usually occurs at a young age.

Causes

The exact reason behind IPF is not known. However, certain risk factors that emanate the issue include smoking, exposure to dust, air pollutants and microaspiration (inhalation of a small amount of foreign material into the lungs while swallowing. It's also known as silent aspiration because it can occur without symptoms) due to reflux disease gastroesophageal reflux disease (GERD) is a condition where stomach contents move up into the oesophagus (the hollow, muscular tube of the alimentary canal that passes food and liquid from the throat to the stomach), causing irritation and other symptoms.

Symptoms

The most common symptoms include shortness of breath and dry cough. This apart, fever, joint pain and weight loss are rarely found in a few.

Age Bar

IPF affects the elderly population more frequently than youngsters. It occurs in the 6th and 7th decade of their life. It is rarely diagnosed in patients aged below 50 years.


Definition Of Hypoxic-Ischemic Injury Of Kidney In Iugr Newborns

Background and Aim: Intrauterine growth restriction (IUGR) is a serious complication of pregnancy leading to an increased risk of perinatal hypoxia, intrauterine and neonatal death.

Circulatory adaptive responses to perinatal hypoxia may lead to renal injury as consequence of decreased perfusion of the kidney. Hypoxic stress usually results a tubulo-interstitial damage in newborns. One of the sensitive biomarker of proximal tubular impairments is a kidney injure molecule-1(KIM-1).

KIM-1 is a transmembrane protein that is not detectable in normal kidney tissue and expressed at very high levels in urine after ischemic and toxic injury.

The aim of this study was to estimate renal function in newborns with IUGR by determination the urinary level of KIM-1.

Methods: Urinary samples of 33 infants with IUGR collected at first 3 days of life to determine urinary KIM-1 concentration. Human KIM Rapid Test was used for this determination.

Results: KIM-1 was detected in urine samples of 20/33 IUGR newborns. Range of urinary level of KIM-1 was 0.5-4 ng/ml. High concentration of this marker was revealed in newborn with pulmonary hypertension and hypoxic encephalopathy. Range of seric creatinine levels was 38-42mkmol/l.

Conclusions: In population of newborns with IUGR feto-neonatal hypoxia can cause kidney impairment which is often not clinically overt. Correlation between urinary level of KIM-1 and severity of perinatal hypoxia indicate prerenal injury of kidney in newborns with IUGR.

Further investigations will be conducted in order to define the correlation between severity of IUGR and levels of KIM-1 and other biomarkers of kidney injury.





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