Why Spirometry Alone Misses the Hidden Lung and Heart Damage of Extreme Preterm Birth

Every year, millions of babies arrive in the world weeks or months before their lungs have finished building the machinery of breathing. Thanks to neonatal intensive care, most of them now survive, including many born at the very edge of viability. But survival is only the first chapter. A growing body of evidence shows that people born extremely preterm carry measurable differences in lung function and cardiovascular health throughout childhood and into adulthood, and that the standard clinical tool used to detect these differences, spirometry, is far too blunt an instrument to capture the full picture. A new commentary in Pediatric Research by Michael L. Beaven of the Kids Research Institute Australia and Paul Finlay of Monash Health argues that the field must move decisively beyond spirometry toward a comprehensive, multi-modal assessment of cardiopulmonary health in preterm-born individuals.

Spirometry, the familiar test in which a patient blows forcefully into a mouthpiece, measures how much air can be exhaled and how quickly. It is cheap, widely available and reproducible, which explains its dominance in both clinics and research studies. Yet it fundamentally measures airflow through large and medium airways. The injury pattern left by extreme preterm birth, often described as chronic lung disease of prematurity or bronchopulmonary dysplasia in its severe forms, is primarily one of disrupted alveolar and vascular development. The distal lung, where gas exchange actually happens, and the pulmonary circulation, which must carry the entire cardiac output through a finely branched vascular tree, are the structures most affected. Spirometry can remain deceptively normal in people whose gas transfer capacity and pulmonary vasculature are substantially impaired.

The evidence for this blind spot is accumulating rapidly. A study by Harris and colleagues, published in Pediatric Research, examined school-aged children born preterm and found that reduced diffusion of carbon monoxide across the lung, a marker of impaired gas exchange surface, was associated with elevated pulmonary artery pressures. This finding is significant because it links two silent abnormalities: a lung that cannot transfer oxygen efficiently and a heart that must pump against higher resistance in the pulmonary circulation. Neither abnormality would necessarily be flagged by a routine spirometry test, and both may progress quietly for decades before producing symptoms.

Longitudinal data reinforce the concern. Research published in the European Respiratory Journal followed individuals born extremely preterm into adulthood and documented persistent deficits in lung diffusion capacity that did not normalize with growth. A systematic review and meta-analysis by Gibbons and colleagues in the European Respiratory Review synthesized findings across lung volumes, gas transfer and oscillometry, a technique that measures airway resistance during quiet tidal breathing rather than forced expiration. Together, these studies sketch a consistent picture: preterm birth leaves a durable imprint on the distal lung and its mechanics that forced expiratory volumes capture only partially, if at all.

The clinical implications extend beyond the lungs. Survivors of extreme preterm birth appear to face elevated long-term risks of pulmonary vascular disease and cardiovascular complications, a concern articulated in a lifespan-oriented framework by Simpson and colleagues in The Lancet Respiratory Medicine. The developing lung and its vasculature are built in tandem during the canalicular and saccular stages of gestation, precisely the window that extreme preterm birth interrupts. When alveolarization is curtailed, the vascular tree that should accompany each new alveolus is curtailed with it. The result is a lung with fewer, larger airspaces and a reduced, remodeled vascular bed, a combination that increases the workload on the right ventricle and may set the stage for pulmonary hypertension and early cardiovascular decline in adult life.

What would a comprehensive assessment look like in practice? The commentary by Beaven and Finlay points toward a battery of complementary tests, each interrogating a different component of the cardiopulmonary system. Lung clearance index, derived from multiple-breath washout, quantifies ventilation inhomogeneity in the small airways and peripheral lung units, and has proven sensitive to early lung disease in other pediatric populations. Body plethysmography measures total lung volumes, revealing the restricted or hyperinflated patterns that spirometry alone can miss. The single-breath or rebreathing diffusing capacity for carbon monoxide directly probes the gas exchange surface. Oscillometry adds information about peripheral airway resistance without requiring maximal effort, an important advantage in young children who cannot reliably perform forced maneuvers.

Cardiovascular assessment deserves equal billing. Echocardiography can estimate pulmonary artery pressures and right ventricular function, while newer techniques such as cardiac magnetic resonance imaging offer precise quantification of right ventricular mass and ejection fraction. Exercise testing integrates the entire system, revealing whether oxygen delivery keeps pace with metabolic demand, and cardiopulmonary exercise testing can unmask limitations that are invisible at rest. Reduced exercise capacity has been documented in preterm-born cohorts, and the physiological basis, whether ventilatory limitation, gas exchange impairment, vascular limitation or deconditioning, can only be disentangled by measuring multiple variables simultaneously during exertion.

The concept of treatable traits offers a compelling rationale for this expanded toolkit. As Zanetto and colleagues argued recently in the American Journal of Respiratory and Critical Care Medicine, clinicians caring for preterm-born individuals with chronic lung disease of prematurity should identify and target specific, modifiable characteristics across the lifespan rather than relying on a single diagnostic label. A patient with preserved spirometry but reduced diffusion capacity and elevated pulmonary artery pressures needs a very different management plan from one with airflow obstruction and air trapping. Without comprehensive phenotyping, the first patient may be falsely reassured and the second may receive therapies that do not address their dominant abnormality. Treatable traits might include airway reactivity, ventilation inhomogeneity, impaired gas transfer, pulmonary vascular dysfunction, muscle weakness and physical deconditioning, each with its own therapeutic levers.

There are practical hurdles to overcome before comprehensive assessment becomes standard care. Many of the recommended tests require specialized equipment, trained personnel and cooperative patients, which limits their availability in ordinary clinical settings and in the low-resource environments where much of the world’s preterm births occur. Reference ranges for children and young adults born preterm are incomplete for several modalities, complicating interpretation. Radiation exposure argues against routine computed tomography, and the research community continues to seek safe, non-invasive imaging surrogates of alveolar and vascular structure. Standardizing protocols across centers and across the age spectrum, from infancy through adulthood, remains an unfinished project, and longitudinal cohorts that follow preterm-born individuals with repeated multi-modal assessments are still relatively rare.

Nevertheless, the direction of travel is clear. The generation born after the widespread adoption of surfactant therapy and gentle ventilation is now reaching adulthood in large numbers, and their long-term cardiopulmonary trajectory is becoming a matter of public health, not just neonatology. Detecting silent gas exchange impairment and early pulmonary vascular change during the school years, when interventions such as exercise programs, vaccination, smoking prevention and targeted follow-up can still alter the course, is far preferable to discovering these problems when symptomatic disease emerges in mid-life. The commentary by Beaven and Finlay makes the case that spirometry, whatever its virtues, cannot carry this burden alone. A comprehensive cardiopulmonary assessment, combining measures of lung volume, ventilation distribution, gas transfer, airway mechanics, pulmonary hemodynamics and exercise capacity, offers the best chance of understanding, monitoring and ultimately improving the lifelong health of the fastest-growing population of adult survivors of neonatal intensive care.

Subject of Research: Cardiopulmonary assessment of lung and cardiovascular outcomes in survivors of extreme preterm birth

Article Title: Beyond spirometry: towards comprehensive cardiopulmonary assessment after extreme preterm birth

Article References: Beaven, M. L., & Finlay, P. (2026). Beyond spirometry: towards comprehensive cardiopulmonary assessment after extreme preterm birth. Pediatric Research. https://doi.org/10.1038/s41390-026-05399-1

Image Credits: AI Generated

DOI: 10.1038/s41390-026-05399-1

Keywords: extreme preterm birth, bronchopulmonary dysplasia, spirometry, lung diffusion capacity, pulmonary hypertension, chronic lung disease of prematurity, lung clearance index, oscillometry, cardiopulmonary exercise testing, treatable traits, pediatric lung function, right ventricular function