A Look at the Potential of Precision Medicine for Pediatric Respiratory Diseases

Patients who were genotyped received montelukast, while those who received standard of care received a long-acting beta agonist (LABA). Analyzes showed that patients who received individualized care had a better quality of life, with a score of 0.16 on the pediatric quality of life questionnaire. “It should be emphasized that the clinical threshold was 0.25, so lower than that, but after 12 months [genotyped patients] seems to be a bit better off, ”said Maitland-van der Zee.

In patients carrying homozygous variants, this effect was more pronounced, marking a sign: “It is likely useful to determine this treatment based on [patients’] genotype, ”she noted. A similar study that will include children aged 6 to 18 aims to provide a clearer answer to this question and will take place in the coming years.

In addition to GWAS, another pathway for potential precision medicine in this population could be the use of exhaled air to assess volatile organic compounds in the lungs of patients. A study on this topic showed “that using a cluster approach it is possible to identify 5 different clusters of pediatric asthma patients by looking at their exhaled air.”

Comparing the clinical features of these patients revealed differences in age group, degree of asthma control and quality of life. “Exhalation says something about the inflammatory phenotype or the asthma phenotype in patients,” explains Maitland-van der Zee.

Similarly, by looking at exhaled air, researchers in the UK were able to develop a sensor technology to identify patients who may or may not be negative for a skin-prick test – a test that checks for immediate allergic reactions to various substances. These results again illustrate the use of exhaled air to help phenotype patients.

According to Maitland-van der Zee, future priorities in this area will include better phenotyping of patients – possibly by combining biomarkers – identifying treatable traits and non-invasive biomarkers, and facilitating early detection. New developments in e-health can also help providers to measure these factors remotely.

After discussing the promise of precision medicine in this area, Ann Chen Wu, MD, MOH, associate professor in the Department of Population Medicine at Harvard Medical School and Harvard Pilgrim Health Care Institute, outlined some of the cost-effectiveness and ethical issues. linked to precision medicine. Chen is also the director of the Center for Healthcare Research in Pediatrics and Precision Medicine Translational Research Center at Harvard Medical School.

A joint statement from ATS and the National Heart, Lung and Blood Institute several years ago concluded that “precision medicine had more value in lung disease because of the introduction of biologics,” Chen explained. Currently, newer biologics target 10% to 15% of patients with severe, persistent asthma among those with asthma.

However, biologics can cost between $ 30,000 and $ 40,000 per patient and must be administered in a hospital setting. But using precision medicine in this area “could help allocate the use of biologics to those who need them and benefit the most,” Chen said.

While precision medicine has potential, a lack of data on minority populations with respiratory disease prevents it from being generalizable to diverse real populations. “Answering questions about the impact of genetic factors on therapeutic drug response in globally diverse populations is essential to make precision medicine socially and scientifically accurate,” she said.

In addition, there are currently no studies that focus solely on the cost-effectiveness of precision medicine for lung diseases. Using a common example of neonatal genomic sequencing, Chen described the unintended positive and negative consequences of genomic testing, including:

Diagnoses in children can lead to family member diagnoses Earlier medical diagnoses and treatments can lead to better outcomes Whole genome sequence can lead to higher health care expenditures without substantial clinical benefits, as unclear results can lead to additional testing and a ‘diagnostic odyssey’

Notably, “systematic reviews of psychological results from single-gene and multi-gene tests suggest that the disclosure of the test does not cause depression or anxiety, as some people have been concerned,” she said.

Given all the potential benefits and costs, better assessments of the value of genomic sequencing for neonates are warranted. But this requires a very large sample size, a long time horizon, and will be expensive.

Since observational data and computational modeling provide an alternative to such studies, Chen and other researchers developed a model to estimate the cost-effectiveness of integrating different genomic sequencing strategies into clinical care.

One version of the model targeted childhood cancer and included a panel of 11 genes. It showed that “among children with the cancer risk variant found in neonatal screening, subsequent surveillance and care would reduce cancer deaths by half before age 20, compared with no screening or usual care.”

Chen continued, “We calculated that universal screening would cost $ 244,000 per year of life gained versus $ 55 per test. We concluded that genetic testing based on the neonatal population can reduce mortality from pediatric cancers and be potentially cost-effective as sequencing costs decrease. “

Determining the cost-effectiveness for lung diseases allows policymakers and insurers to decide whether to cover the cost of the test, while finding new findings of genetic variants or genes can change their interpretation. “For example, a variant that was thought to be related to a disease could have a new benign interpretation,” said Chen. This scenario poses a different challenge, as it is still not known ethnically how much time should be allocated to communicate updated information to patients or whose job it is to educate patients about these changes in interpretation.

“Precision medicine for pediatric lung disease has great potential, but we still have a long way to go,” Chen concluded. “Assessing cost-effectiveness, generalizability to diverse populations and ethical considerations increases the likelihood of translation to clinical practice.”

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