Genetic discovery could be 'tip of the iceberg' to better understand lung disease among Inuit | Canada News Media
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Genetic discovery could be ‘tip of the iceberg’ to better understand lung disease among Inuit

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In his years as a pediatric respirologist at CHEO, Dr. Tom Kovesi had cared for many children with severe respiratory illnesses. But one patient stood out.

Kovesi, who is also an investigator with the CHEO Research Institute, had been following the Inuk girl from Nunavut since she was a baby. CHEO is the tertiary centre for children from Nunavut. She had struggled through recurring bouts of severe pneumonia and serious ear infections.

Her condition was so severe that it was consistent with the rare disease known as primary cilliary dyskinesia, or PCD, which Kovesi describes as a “cousin” of cystic fibrosis. But the belief had always been that Inuit populations, which have among of the highest rates of lung disease in the world, did not have PCD.

That belief was based on previous research using less advanced diagnostic techniques than are currently available. In search of more information about her illness, Kovesi used an electron microscope to determine whether she had PCD, but the results were normal. Not satisfied, he tried genetic testing and that is where he found an answer: a never-before-discovered gene variant that causes PCD. He repeated the test at a second lab to be certain.

Once she was given treatment for PCD, her condition began to stabilize. The girl from Nunavut became Patient Zero for a new discovery that could have profound implications for treatment and better understanding of lung disease among members of the Inuit populations in Canada and elsewhere.

Genetic testing on other Inuit patients found others with the genetic marker for PCD.

Meanwhile, Dr. Adam Shapiro, an investigator in the Child Health and Human Development Program at the research institute of McGill University and a pediatric respirologist at Montreal Children’s Hospital, also found the gene variant in some patients.

Kovesi and Shapiro are co-senior authors of a paper published in the journal Pediatric Pulmonology that reports on seven Inuit patients with PCD identified through genetic testing.

The findings, in a gene called DNAH11 in Inuit individuals from both Nunavik in northern Quebec and Nunavut, suggest that the disease may be “quite common among Inuit and may be an important cause of lung disease in this population,” said Kovesi.

The research should lead to routine testing for Inuit with recurrent pneumonia and/or chronic lung disease to determine whether they have PCD, the authors wrote. Kovesi also said routine newborn screening for PCD through genetic analysis should be considered in Inuit regions.

Diagnosing PCD is important, Kovesi said, because treatments — similar to therapies to treat cystic fibrosis — are available. Treatment includes daily airway clearance and the use of antibiotics to prevent infections, among other things.

Primary ciliary dyskinesia, or PCD, is a rare disease that affects the tiny, hair-like structures (cilia) that line the airways. Cilia move together in wavelike motions. That motion carries mucus toward the mouth or nose to be coughed or sneezed out of the body.

But in patients with PCD, cilia do not work the same way to move mucus out of the body, which can cause breathing problems and recurrent infections.

PCD affects about one in 20,000 Canadians, but in Inuit populations, that number is estimated to be closer to one in 1,400, although more research is needed, say the authors of the paper.

Inuit populations have high rates of lung disease, including the highest known rates of respiratory syncytial virus (RSV) for children in the first year of life and high rates of tuberculosis.

“We see so much lung disease in the Inuit and it is so severe, it is disproportionate,” said Shapiro.

The genetic findings do not explain all of the lung disease in the Inuit population, he said, “but it explains some of it.”

Other key factors contributing to lung disease in Inuit populations include crowded and poorly ventilated housing and poverty.

Shapiro noted that out of 40 children being followed at Montreal Children’s Hospital for severe chronic lung disease, the majority do not have PCD.

Both Shapiro and Kovesi said more work needs to be done, not only to treat patients, but to better understand the genetic causes of chronic lung disease.

“I think this is the tip of the iceberg,” said Shapiro. “It will open the floodgates for more genetic work.”

Kovesi said better understanding of the prevalence of PCD caused by genetic variants in the gene DNAH11 and possibly other genes in the Inuit population will require more research. The work, he said, is an important step “towards improved delivery of care to affected Inuit families.”

onlinelibrary.wiley.com/doi/10.1002/ppul.26414

 

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Whooping cough is at a decade-high level in US

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MILWAUKEE (AP) — Whooping cough is at its highest level in a decade for this time of year, U.S. health officials reported Thursday.

There have been 18,506 cases of whooping cough reported so far, the Centers for Disease Control and Prevention said. That’s the most at this point in the year since 2014, when cases topped 21,800.

The increase is not unexpected — whooping cough peaks every three to five years, health experts said. And the numbers indicate a return to levels before the coronavirus pandemic, when whooping cough and other contagious illnesses plummeted.

Still, the tally has some state health officials concerned, including those in Wisconsin, where there have been about 1,000 cases so far this year, compared to a total of 51 last year.

Nationwide, CDC has reported that kindergarten vaccination rates dipped last year and vaccine exemptions are at an all-time high. Thursday, it released state figures, showing that about 86% of kindergartners in Wisconsin got the whooping cough vaccine, compared to more than 92% nationally.

Whooping cough, also called pertussis, usually starts out like a cold, with a runny nose and other common symptoms, before turning into a prolonged cough. It is treated with antibiotics. Whooping cough used to be very common until a vaccine was introduced in the 1950s, which is now part of routine childhood vaccinations. It is in a shot along with tetanus and diphtheria vaccines. The combo shot is recommended for adults every 10 years.

“They used to call it the 100-day cough because it literally lasts for 100 days,” said Joyce Knestrick, a family nurse practitioner in Wheeling, West Virginia.

Whooping cough is usually seen mostly in infants and young children, who can develop serious complications. That’s why the vaccine is recommended during pregnancy, to pass along protection to the newborn, and for those who spend a lot of time with infants.

But public health workers say outbreaks this year are hitting older kids and teens. In Pennsylvania, most outbreaks have been in middle school, high school and college settings, an official said. Nearly all the cases in Douglas County, Nebraska, are schoolkids and teens, said Justin Frederick, deputy director of the health department.

That includes his own teenage daughter.

“It’s a horrible disease. She still wakes up — after being treated with her antibiotics — in a panic because she’s coughing so much she can’t breathe,” he said.

It’s important to get tested and treated with antibiotics early, said Dr. Kris Bryant, who specializes in pediatric infectious diseases at Norton Children’s in Louisville, Kentucky. People exposed to the bacteria can also take antibiotics to stop the spread.

“Pertussis is worth preventing,” Bryant said. “The good news is that we have safe and effective vaccines.”

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AP data journalist Kasturi Pananjady contributed to this report.

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The Associated Press Health and Science Department receives support from the Robert Wood Johnson Foundation. The AP is solely responsible for all content.

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Scientists show how sperm and egg come together like a key in a lock

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How a sperm and egg fuse together has long been a mystery.

New research by scientists in Austria provides tantalizing clues, showing fertilization works like a lock and key across the animal kingdom, from fish to people.

“We discovered this mechanism that’s really fundamental across all vertebrates as far as we can tell,” said co-author Andrea Pauli at the Research Institute of Molecular Pathology in Vienna.

The team found that three proteins on the sperm join to form a sort of key that unlocks the egg, allowing the sperm to attach. Their findings, drawn from studies in zebrafish, mice, and human cells, show how this process has persisted over millions of years of evolution. Results were published Thursday in the journal Cell.

Scientists had previously known about two proteins, one on the surface of the sperm and another on the egg’s membrane. Working with international collaborators, Pauli’s lab used Google DeepMind’s artificial intelligence tool AlphaFold — whose developers were awarded a Nobel Prize earlier this month — to help them identify a new protein that allows the first molecular connection between sperm and egg. They also demonstrated how it functions in living things.

It wasn’t previously known how the proteins “worked together as a team in order to allow sperm and egg to recognize each other,” Pauli said.

Scientists still don’t know how the sperm actually gets inside the egg after it attaches and hope to delve into that next.

Eventually, Pauli said, such work could help other scientists understand infertility better or develop new birth control methods.

The work provides targets for the development of male contraceptives in particular, said David Greenstein, a genetics and cell biology expert at the University of Minnesota who was not involved in the study.

The latest study “also underscores the importance of this year’s Nobel Prize in chemistry,” he said in an email.

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The Associated Press Health and Science Department receives support from the Howard Hughes Medical Institute’s Science and Educational Media Group. The AP is solely responsible for all content.

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Older patients, non-English speakers more likely to be harmed in hospital: report

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Patients who are older, don’t speak English, and don’t have a high school education are more likely to experience harm during a hospital stay in Canada, according to new research.

The Canadian Institute for Health Information measured preventableharmful events from 2023 to 2024, such as bed sores and medication errors,experienced by patients who received acute care in hospital.

The research published Thursday shows patients who don’t speak English or French are 30 per cent more likely to experience harm. Patients without a high school education are 20 per cent more likely to endure harm compared to those with higher education levels.

The report also found that patients 85 and older are five times more likely to experience harm during a hospital stay compared to those under 20.

“The goal of this report is to get folks thinking about equity as being a key dimension of the patient safety effort within a hospital,” says Dana Riley, an author of the report and a program lead on CIHI’s population health team.

When a health-care provider and a patient don’t speak the same language, that can result in the administration of a wrong test or procedure, research shows. Similarly, Riley says a lower level of education is associated with a lower level of health literacy, which can result in increased vulnerability to communication errors.

“It’s fairly costly to the patient and it’s costly to the system,” says Riley, noting the average hospital stay for a patient who experiences harm is four times more expensive than the cost of a hospital stay without a harmful event – $42,558 compared to $9,072.

“I think there are a variety of different reasons why we might start to think about patient safety, think about equity, as key interconnected dimensions of health-care quality,” says Riley.

The analysis doesn’t include data on racialized patients because Riley says pan-Canadian data was not available for their research. Data from Quebec and some mental health patients was also excluded due to differences in data collection.

Efforts to reduce patient injuries at one Ontario hospital network appears to have resulted in less harm. Patient falls at Mackenzie Health causing injury are down 40 per cent, pressure injuries have decreased 51 per cent, and central line-associated bloodstream infections, such as IV therapy, have been reduced 34 per cent.

The hospital created a “zero harm” plan in 2019 to reduce errors after a hospital survey revealed low safety scores. They integrated principles used in aviation and nuclear industries, which prioritize safety in complex high-risk environments.

“The premise is first driven by a cultural shift where people feel comfortable actually calling out these events,” says Mackenzie Health President and Chief Executive Officer Altaf Stationwala.

They introduced harm reduction training and daily meetings to discuss risks in the hospital. Mackenzie partnered with virtual interpreters that speak 240 languages and understand medical jargon. Geriatric care nurses serve the nearly 70 per cent of patients over the age of 75, and staff are encouraged to communicate as frequently as possible, and in plain language, says Stationwala.

“What we do in health care is we take control away from patients and families, and what we know is we need to empower patients and families and that ultimately results in better health care.”

This report by The Canadian Press was first published Oct. 17, 2024.

Canadian Press health coverage receives support through a partnership with the Canadian Medical Association. CP is solely responsible for this content.

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