For over 15 years, Dr Anthony Shum, a pulmonologist at the University of California, San Francisco has been studying a rare genetic disorder called the COPA Syndrome. It stands for coatomer subunit alpha and is a rare, inherited disorder that affects the lungs, joint, and kidney. The National Organization for Rare Disorder also notes that it is a genetic autoimmune disorder that is caused by mutations in the COPA gene. This disease affects families unpredictably—some individuals with the mutation develop severe lung damage early in life, while others remain completely healthy. Now, Shum’s team has discovered a protective genetic variant that may offer new hope for treatment.

A Breakthrough

Researchers found that some relatives of COPA Syndrome patients stayed healthy despite carrying the same COPA gene mutation that causes the disease. The key difference? These unaffected individuals had a protective version of another gene called HAQ-STING.

When scientists introduced HAQ-STING into diseased lung cells from COPA patients, the cells returned to a balanced state, suggesting that this gene could be used as a therapy.

“We really think HAQ-STING could be a gene therapy tool and a step toward a cure,” said Shum, whose findings were published in the Journal of Experimental Medicine.

Families Who Solved The Mystery

Shum’s journey into COPA Syndrome research began in 2011 when he treated a young woman, Letasha, who had severe lung bleeding. Her mother, Betty Towe, mentioned that Letasha’s sister, Kristina, had suffered from similar symptoms. Over the years, Betty had taken both daughters on a four-hour trip to UCSF for treatment. After tracing their family history, Shum discovered that their distant relatives in Texas and Oakland also had lung problems and arthritis. In 2015, Shum, along with scientists from Baylor College of Medicine and Texas Children’s Hospital identified the COPA gene mutation. They realized that it was the common factor behind the illness. However, only some of the 30 individuals with the mutation actually developed symptoms, leaving a major question unanswered.

The Domino Effect

It was established that it occurs when a mutated COPA gene causes another gene STING to go overdrive. The STING that helps fight infections in COPA patients, remain permanently active, which leads to chronic inflammation that damages the lungs, kidneys, and joints. In 2020, while studying STING’s role in the disease, researchers discovered a key variation: HAQ-STING. This version of STING, present in about one-third of the population, appeared to neutralize the harmful effects of the COPA mutation.

To confirm their theory, the scientists needed both affected and unaffected family members to participate in the testing. Letasha, Kristina and Betty immediately volunteered. The researchers then analyzed DNA samples from 26 COPA patients and their healthy relatives. They also conducted CT scans and blood tests to ensure that unaffected members did not have any hidden symptoms. When the findings were all clear, it was revealed that all the healthy individuals had HAQ-STING, while none of the COPA patients did. This was the first known case of a common gene variant completely protecting against a severe genetic disease.

Encouraged by this discovery, researchers tested HAQ-STING’s effects in a lab setting. They introduced it into diseased lung cells from COPA patients, and the cells returned to normal function.

Way Ahead

Shum believes HAQ-STING could lead to game-changing treatments, including:

• Prenatal gene therapy for babies diagnosed with COPA Syndrome before birth
• Aerosol delivery of HAQ-STING for adults, directly targeting the lungs

Before publishing their findings, Shum called Betty with the news—her own HAQ-STING gene had protected her from the disease. He also informed Letasha and Kristina, who were overwhelmed with relief and joy.

“We always believed Dr. Shum would get to the bottom of it,” said Letasha. “This discovery is going to change lives.”

Dry cough and breathing difficulty aren’t always caused by asthma, COPD, or infections. They can also be signs of interstitial lung disease (ILD), a group of lung conditions that can cause inflammation and scarring and, in some cases, progressive loss of lung function.

ILD can go unnoticed in its early stages because its symptoms are often mistaken for more common respiratory conditions. By the time a patient undergoes a CT scan and reaches an ILD clinic, significant lung scarring may have already developed — and some of that damage may be irreversible.

Millions May Be Living With ILD Worldwide

A Global Burden of Disease Study 2023 analysis, published in December 2025, estimated that 4.58 million people were living with ILD and pulmonary sarcoidosis worldwide in 2023, with 112,650 deaths attributed to the conditions that year.

“The true global burden of ILD is higher than currently reported, particularly in underserved populations and low- and middle-income countries,” Prof. Marlies Wijsenbeek-Lourens, Pulmonologist and Head of the Center for Interstitial Lung Diseases and Sarcoidosis at Erasmus University Medical Center, Netherlands, told HealthandMe.

The global expert said most available epidemiological data come from Europe, North America, Japan, South Korea and Australia, where access to specialist care, multidisciplinary diagnosis and high-resolution CT imaging is generally more available.

“As a result, large parts of Africa, South America, South and Southeast Asia remain underrepresented in current estimates. In these regions, more limited access to diagnostic facilities, fewer ILD specialists and under-recognition of disease undoubtedly result in substantial underdiagnosis.”

Even in high-income countries, she added, some patients with ILD likely remain undiagnosed because symptoms such as breathlessness and cough are often attributed to more common conditions.

Also read: From Occasional to Long-Term Smoking, Experts Explain How Much Lung Damage Can Actually Reverse After Quitting?

What Is Interstitial Lung Disease?

ILD is not a single disease but a group of more than 200 lung conditions. The disease affects the interstitium, the tissue surrounding and supporting the lungs’ air sacs, or alveoli. In ILD, this tissue can become inflamed and/or scarred.

As scarring progresses, the lungs can become stiffer, making it harder for them to expand and reducing the efficiency of oxygen transfer. As the disease progresses, the lung shrinks, making it difficult for the patient to breathe.

According to Prof. Marlies, there is a rise in ILD diagnoses due to several factors, such as:

• Better awareness
• More HRCT scans
• Better diagnosis
• Ageing populations
• Autoimmune disease
• Environmental and occupational exposure.

When Should Doctors Suspect ILD?

Some forms of ILD can be treated more effectively when identified early, before permanent lung damage occurs.

“Unfortunately, many patients still reach an ILD specialist late. Breathlessness and cough may initially be treated as asthma, infection or sometimes even tuberculosis. By the time a CT scan is done and the patient reaches an ILD clinic, significant scarring may already have developed,” Dr Asmita Mehta, Professor and Head, Department of Respiratory Medicine at Amrita Institute of Medical Sciences, Kochi, told HealthandMe.

“A dry cough and gradually progressive breathlessness lasting for more than three months, particularly breathlessness while walking or climbing stairs, should raise suspicion of ILD rather than simply being attributed to asthma, infection or ageing,” she added.

Doctors should think of ILD especially when these symptoms do not improve with usual treatment, when fine crackling sounds are heard in the lungs, or when oxygen levels fall during walking.

It is also important to ask about joint pain, skin changes, dry eyes or mouth, and exposure to birds, mould, biomass smoke or occupational dust. Sometimes the clue to ILD is outside the lungs, the expert said.

ILD And COVID-19

Pre-existing ILD was associated with worse outcomes during COVID-19. Now, six years later, some patients who had severe COVID-19 also continue to show persistent lung abnormalities.

“The reassuring part is that not every abnormal CT after COVID means progressive lung fibrosis. In many patients, the lung changes gradually improve or remain stable. Some patients who had very severe COVID, prolonged ICU admission, or required ventilation may be left with persistent scarring and may need longer follow-up,” Dr Asmita said.

What Does ILD Look Like In India?

Common ILD diagnoses seen in India include connective tissue disease-associated ILD (CTD-ILD), hypersensitivity pneumonitis (HP), idiopathic pulmonary fibrosis (IPF), sarcoidosis and idiopathic nonspecific interstitial pneumonia (NSIP).

Dr Asmita said that, apart from idiopathic pulmonary fibrosis, ILD related to autoimmune diseases and environmental exposures is also commonly seen in India. These exposures can include birds, mould, biomass smoke and certain occupations.

Epidemiological reviews estimate the overall prevalence of ILD in India to range between 49.0 and 98.1 per 100,000 people, with an annual crude incidence rate of 10.1 to 20.2 per 100,000 population.

India is also building a larger national evidence base through the ICMR-led Indian Network of Pulmonary Fibrosis (INPF) registry.

Biggest Challenges For ILD Patients In India

• Delayed diagnosis: Symptoms can be mistaken for asthma, infections, or tuberculosis.
• Limited specialist access: ILD specialists and advanced diagnostic facilities are concentrated in larger centres.
• High treatment costs: Medicines, investigations, oxygen, and pulmonary rehabilitation can be expensive.
• Limited transplant access: Lung transplantation remains available only to a limited number of eligible patients.
• Low awareness: Many patients and families are unfamiliar with ILD and its long-term nature.

“We therefore need not only earlier diagnosis, but better awareness, affordable treatment, wider access to ILD specialists and stronger advanced-care and transplant programs,” Dr Asmita said.

Humans and most mammals have two sex chromosomes, X and Y. Females typically have two X chromosomes (XX), while males typically have one X and one Y chromosome (XY). As men age, many of their cells gradually lose the Y chromosome, due to a common genetic change.

Research has shown that cancer incidence and mortality rate are more among men than women. A new study may offer clues as to why.

Researchers from the University of Arizona found that loss of the Y chromosome in men’s tissues could create conditions that allow cancer to develop.

The research, published in JCI Insights, found that Y chromosome loss creates a pre-neoplastic field effect — a hidden zone of genetic vulnerability in normal-appearing tissue that may provide fertile ground for cancer development.

What Did The Study Find?

Also read: US Cancer Death Rates Fall For Men, Women: Lung Cancer Progress Drives Decline

Previous studies have linked loss of the Y chromosome in blood cells to an increased risk of disease. The new study systematically profiled Y chromosome loss across normal, precancerous and cancerous tissues from 11 major human organs.

“We were able to show that the loss of the Y chromosome is found in normal-appearing tissues adjacent to a tumor,” said physician-scientist Dr. Dan Theodorescu of the University of Arizona Cancer Center.

“That finding is what makes this discovery so exciting. It suggests we may be looking at one of the earliest signposts of cancer forming.”

The team analyzed 1,000 tissue samples from 405 men, using an automated fluorescent imaging system to examine more than 4.3 million individual cell nuclei and measure the ratio of Y to X chromosomes.

In one part of the study, researchers created detailed maps of bladder tissue removed during cancer surgery.

The maps showed that Y chromosome loss increased as tissue progressed from normal tissue to early abnormal cells and then to cancer.

Y chromosome loss in normal-appearing tissue was highest in samples from colon, rectal, esophageal, pancreatic and lung cancers.

“We are now thinking of this as a gradient, similar to a hillside that slowly gets steeper,” Theodorescu said. “The closer the tissue is to a cancer, the more Y chromosome loss we see. That gradient could one day help doctors suspect trouble in biopsies that miss a smaller cancer.”

How Y Chromosome Loss May Affect Cancer

Read More: UK NHS Trust To Review 4,500 More Breast Cancer Cases After 20 Unnecessary Mastectomies

Theodorescu’s previous research examined how loss of the Y chromosome in cancer cells can help them evade the immune system. This may help explain why Y chromosome loss has been associated with higher mortality from certain carcinomas.

What Does The Y Chromosome Do?

The Y chromosome spans more than 59 million DNA base pairs and accounts for almost 2% of the DNA in human cells. It contains roughly 70 to 200 genes involved in protein production.

The chromosome contains genes that play important roles in male sex development and fertility, including sperm production.

Beyond reproduction, research suggests that the Y chromosome can influence immune and inflammatory responses in men, potentially affecting susceptibility to certain diseases.

READ: Multicancer Blood Test Detects 17 Cancer In A Large Study: Can It Replace Mammograms & Colonoscopies?

Cancer Risk In Men

Globally, cancer is diagnosed more often in men than in women, with men having roughly a 25% higher incidence rate. Men also account for a greater share of cancer deaths worldwide.

Some of the most common cancers affecting men include prostate, lung, colorectal and skin cancers. Early detection and appropriate screening can improve the chances of successful treatment for several types of cancer.

Shortness of breath can happen for many reasons. Low activity, extra pounds and long hours of sitting can all play a role. But ongoing symptoms may be due to asthma or other lung problems. It can be linked to anemia as well. Heart problems are another possibility, along with other conditions that involve the lungs or the heart and blood flow. Sometimes breathing trouble shows up before other clear signs appear.

Why Do You Feel Breathless

A clinician will try to sort out what is going on by looking at your pattern of symptoms. They may ask how fast it happens, when it begins and if it’s getting worse over time. They also inquire about other symptoms, such as pain or tightness in the chest, a persistent cough, wheezing, feeling lightheaded, unusual tiredness or swelling of the legs. A careful history and a physical exam can guide the next steps and whether tests are needed.

More detailed checks are now available for breathlessness that has no clear cause. What gets done depends on what the doctor suspects. You might have oxygen level checks, blood tests, breathing tests, chest scans, an ECG, or an echocardiogram. In some cases, doctors may suggest a more focused look at the airways, such as bronchoscopy, or other procedures to find a specific problem and address it.

Try not to panic every time you feel short of breath. Instead, pay attention to how your breathing has been changing from your normal pattern. If simple daily tasks that used to feel fine suddenly make you unusually breathless, or if the symptoms do not go away and start to get worse, it is a good idea to get checked by a clinician. Getting help sooner can support an early look at what is causing it and can help set up the right care.

(By Dr Anjan Siotia, Director of Cardiology at BM Birla Heart Hospital)