PLD & Phenotypes

Prematurity-associated lung disease is not one uniform condition

RHiNO research has helped show that respiratory disease after preterm birth is heterogeneous. Rather than relying on symptoms or neonatal labels alone, the PLD framework asks what current physiological pattern an individual has, how it arose, whether it is reversible, and how it may evolve with growth.

Our discoveries Publications

Illustrated overview of PTc, POLD, pPRISm and pDysanapsis phenotypes.

Why PLD?

Moving beyond bronchopulmonary dysplasia alone

Bronchopulmonary dysplasia (BPD) remains an important neonatal diagnosis, but it does not fully capture the diversity of later respiratory abnormalities seen in children and adults born preterm. RHiNO work therefore uses the concept of prematurity-associated lung disease (PLD) to describe later respiratory impairment more broadly and more physiologically.

Key principle: PLD is defined by present respiratory physiology, not by neonatal history alone.

The spirometric framework

Four patterns based on FEV₁ and FEV₁/FVC

A practical way to classify later respiratory physiology after preterm birth is to consider whether FEV₁ and FEV₁/FVC are above or below the lower limit of normal (LLN). This yields one preterm control pattern and three abnormal phenotypes.

PTc

Preterm control pattern

FEV₁ ≥ LLN
FEV₁/FVC ≥ LLN

This is the preserved physiological reference pattern among preterm-born participants.

POLD

Prematurity-associated obstructive lung disease

FEV₁ < LLN
FEV₁/FVC < LLN

An obstructive pattern suggesting airflow limitation, with potential links to later chronic obstructive disease.

pPRISm

Preserved ratio impaired spirometry

FEV₁ < LLN
FEV₁/FVC ≥ LLN

Reduced expiratory volume despite a preserved ratio, implying physiology distinct from classical obstruction.

pDysanapsis

Prematurity-associated dysanapsis

FEV₁ ≥ LLN
FEV₁/FVC < LLN

A pattern compatible with airway–lung size mismatch, where ratio is reduced despite preserved FEV₁.

Why phenotype?

Phenotypes help connect physiology with mechanism, prognosis and treatment

Mechanism

Different phenotypes may arise from different developmental abnormalities in airways, alveoli or airway–lung matching.

Reversibility

Bronchodilator responsiveness is not uniform across PLD phenotypes, so “abnormal lung function” is not a sufficient treatment guide.

Trajectory

Some physiological patterns may be more stable over time, while others may transition as lungs continue to grow.

Management

A phenotype-based framework creates a more rational route to treatment, monitoring and future interventional research.

Bronchodilator response

PLD is not necessarily fixed disease

Single-dose bronchodilator testing has shown that a substantial proportion of abnormal pre-bronchodilator spirometry moves into the preterm-control range after treatment. Importantly, this reclassification differs across phenotypes, suggesting that the reversibility of PLD is heterogeneous.

Some abnormal physiology is reversible.
Reversibility varies by physiological phenotype.
This has implications for diagnosis, follow-up and treatment selection.

Clinical implication

A child born preterm with abnormal spirometry should not automatically be assumed to have fixed impairment. Phenotyping and bronchodilator testing provide more clinically meaningful information than a single uncontextualised FEV₁ measurement.

Across the life course

PLD is a framework for trajectories, not just a label

The most important question is increasingly not simply whether lung function is abnormal, but how a phenotype changes over time. RHiNO is therefore increasingly focused on longitudinal stability, transition between phenotypes, and the relationship between childhood physiology and later respiratory health.

Preterm birthDisrupted lung development

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Childhood phenotypePTc, POLD, pPRISm, pDysanapsis

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Growth and transitionPersistence, reversibility or change

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Adult respiratory healthPotential future chronic disease risk

Illustration showing progression from premature birth to lung development and later childhood outcomes.

Why this matters now

PLD changes how we think about respiratory follow-up after preterm birth

A phenotype-based PLD framework supports more precise follow-up and future treatment studies. It also provides a bridge between neonatal respiratory history, childhood physiology and adult lung-health research.

This is one reason why PLD and its phenotypes were brought together in the 2026 Lancet Respiratory Medicine Series.

Explore the PLD Series

Explore related pages