Asthma study tracking Tucsonans from birth into adulthood

Asthma and chronic obstructive pulmonary disease, or COPD, are potentially life-threatening lung conditions that make it difficult to breathe. Around 40 years ago, there were theories that asthma and COPD could have causes originating in early life, but they were just that – theories. 

Image

“Researchers asked 70 year olds with COPD if they remembered having childhood respiratory difficulties,” said Fernando D. Martinez, MD, director of the University of Arizona Health Sciences Asthma and Airway Disease Research Center and Regents Professor of pediatrics in the College of Medicine – Tucson. “Many of them remembered having asthma, or being hospitalized with pneumonia, but we know a person’s memory is not always reliable that far back.”

In 1980, researchers at the Asthma and Airway Disease Research Center launched a study focused on exploring the early-life origins of asthma. From 1980 to 1984, 1,246 healthy babies were enrolled into the Tucson Children’s Respiratory Study. Martinez joined the research team only a few years later, and researchers are still following more than 700 of those babies, who are now adults in their 40s. 

“We’ve collected data as some of them developed asthma, and we are still collecting data as some of them are now showing signs of COPD,” Martinez said. “The Tucson Children’s Respiratory Study has contributed so much of what the scientific community knows about asthma. The importance of early-life influences is confirmed over and over again.” 

Discoveries start with data 

One of the main functions of the lungs is to take oxygen out of the air and pass it into the bloodstream. When a person inhales, air enters the lungs and travels through a series of progressively smaller airways until reaching tiny air sacs surrounded by blood vessels. This is where oxygen from the air is diffused into the bloodstream.

When a person has asthma, their airways become inflamed and sensitive to triggers such as allergens or infections. The airways tighten and fill with mucus, leading to symptoms including wheezing, coughing and shortness of breath.

When a person has COPD, which includes chronic bronchitis and emphysema, chronic inflammation of the airways causes them to become obstructed. This is usually caused by long-term exposure to irritants such as cigarette smoke.

Asthma can develop at any age, while COPD is usually diagnosed after age 50.

Image

“There are many heavy smokers who never develop COPD, and there are many people who have allergies who are not asthmatic,” said Martinez, who is a member of the university’s BIO5 Institute. “We wanted to narrow down a common thread, such as the incidence of a severe lower respiratory infection, like bronchiolitis or pneumonia, in early life.”

To learn and observe as much as possible from this large group of infants, researchers gathered a wide variety of physiological data going all the way back to cord blood in some cases. Children were examined for conditions including bronchiolitis, pneumonia and croup, and symptoms and causes documented. In some cases, family members were also surveyed and tested. In-depth evaluations of study participants at ages 6, 11, 16, 22, 26, 32, 36 and 40 measured their lung function. Allergy skin prick tests were taken to test for local allergens that might trigger asthma. Blood samples were collected for complete blood cell counts, DNA extraction and total immunoglobin E tests, the latter of which measure an antibody that is often more prevalent in people with allergies. 

“The beauty of how this study was designed is that it is not based on participants having any condition or disease before they were enrolled. Instead, we have a large group recruited at birth, and we just follow them over time,” said Stefano Guerra, MD, PhD, MPH, study co-lead, director of the Asthma and Airway Disease Research Center’s Population Science Unit and professor in the College of Medicine – Tucson.

Tucson Children’s Respiratory Study data has been used to describe various wheezing disorders, develop an Asthma Predictive Index and evaluate a large number of risk factors for acute respiratory tract illnesses. Other findings include day care attendance being associated with greater immune protection later in childhood, children with older siblings in the house having a reduced risk for asthma and frequent wheezing, and breast feeding possibly protecting infants from recurrent ear infections. 

“The data collected in the Tucson Children’s Respiratory Study can be used for almost any idea or hypothesis you can think of involving lung function or any of the other variables measured,” Guerra said.

A generation’s worth of data 

Data collected over decades is proving to be invaluable for new studies into other lung conditions. 

“We recently used Tucson Children’s Respiratory Study data for a study on another type of respiratory impairment called spirometric restriction, which means a person’s lungs don’t expand fully,” Guerra said. “The data showed that poor growth and nutritional deficits before birth and during childhood precede and predict the development of this condition.” 

Tara Carr, MD, a Professor of Medicine at the College of Medicine—Tucson, sees patients in the Allergy and Immunology Clinic at Banner – University Medical Center Tucson. One of her studies examined the interconnected public health challenges of asthma and obesity. She used data from the Tucson Children's Respiratory Study to show that higher insulin levels at age 6 resulted in a twofold higher risk of asthma occurrence. 

“The beauty of how this study was designed is that it is not based on participants having any condition or disease before they were enrolled.” — Stefano Guerra, MD, PhD, MPH

In the ’80s, the Tucson Children Respiratory Study collected blood samples on these young children and carefully stored the samples in deep freezers for future analysis,” Carr said. “This allowed us to take those samples out and measure for insulin levels some 30 years later. We found that the higher insulin levels coincided with higher risk of asthma, even if the child wasn’t overweight at the time.”

Carr, who happened to be born around the same year as many of the participants, marveled at the forward thinking involved in the creation of the Tucson Children’s Respiratory Study. 

“These researchers were innovative in so many ways,” she said. “To select from a pool of healthy babies from the onset, to follow up with them so regularly, to record their health outcomes at doctor visits, and to gather all these objective measurements for over 40 years is just brilliant.” 

For Martinez, a practicing pediatric pulmonologist at Banner Health’s Diamond Children’s Multispecialty Services Clinic in Tucson, studying childhood influences on health always seemed intuitive. 

“There’s a saying that where the twig is bent, so inclined is the tree. The idea is the earlier the tree bends, the more it is going to curve in that direction as it grows,” he said. 

Martinez said future studies will examine the genetic factors persistent in asthma and COPD, as well as other determinants of lung-function decline in adult life.

The Tucson Children’s Respiratory Study babies are now middle-aged adults. Thanks to their extended participation and scientists’ commitment to the project, the research – and the discoveries –  will continue to help millions of people with asthma and COPD for decades to come.