Journal of Pulmonology and Respiratory Diseases
Open Access

Bronchopulmonary dysplasia (BPD); Premature infants; Long-term pulmonary outcomes; Alveolar development; Chronic respiratory symptoms; Pulmonary function.

Introduction

Bronchopulmonary dysplasia (BPD) is a major complication of preterm birth, first described in 1967 by Northway et al. It primarily affects infants born before 32 weeks of gestation who require prolonged respiratory support. Despite advances in neonatal care, BPD remains prevalent, affecting up to 50% of infants born before 28 weeks of gestation [1]. The pathophysiology of BPD involves disrupted alveolar development, inflammation, and fibrosis, leading to long-term pulmonary sequelae.

Objectives

This review aims to provide a comprehensive overview of the long-term pulmonary outcomes in infants diagnosed with BPD, focusing on:

• Pulmonary function.
• Respiratory symptoms.
• Health-related quality of life.
• Implications for clinical practice and future research.

Pathophysiology of BPD

Alveolar development and injury

The development of the alveoli is disrupted in infants with BPD, characterized by fewer and larger alveoli, leading to impaired gas exchange. Key factors contributing to this disruption include

Hyperoxia: Prolonged exposure to high oxygen levels can cause oxidative stress and inflammation.

Mechanical Ventilation: Ventilation-induced lung injury can exacerbate inflammation and disrupt alveolarization.

Infection and Inflammation: Prenatal and postnatal infections can trigger inflammatory responses that impair lung development [2,3].

Inflammatory pathways

Inflammation plays a central role in the pathogenesis of BPD. Cytokines such as IL-6, IL-8, and TNF-α are elevated in the lungs of infants with BPD, leading to chronic inflammation and fibrosis. This inflammatory milieu contributes to the long-term pulmonary sequelae observed in these patients.

Long-term pulmonary outcomes

• Pulmonary function

Spirometry and lung volumes

Studies have consistently shown that individuals with a history of BPD have reduced lung function persisting into childhood and adulthood. Key findings include:

Reduced FEV1: Forced expiratory volume in one second (FEV1) is often significantly lower in individuals with BPD, indicating obstructive airway disease.

Decreased FVC: Forced vital capacity (FVC) is also reduced, reflecting restrictive lung disease.

Lowered Diffusion Capacity: Impaired alveolar-capillary gas exchange is evident from reduced diffusion capacity (DLCO) [4].

Airway hyperreactivity

Airway hyperreactivity is common in BPD survivors, with increased bronchial responsiveness to stimuli such as methacholine. This hyperreactivity can lead to increased symptoms and exacerbations.

Respiratory symptoms

Chronic respiratory symptoms

Children and adults with a history of BPD often experience chronic respiratory symptoms, including:

Wheezing: Persistent wheezing is a common complaint, often exacerbated by respiratory infections.

Cough: Chronic cough, particularly in response to exertion or environmental triggers [5].

Dyspnea: Shortness of breath, especially during physical activity, is frequently reported.

Exacerbations and hospitalizations

Individuals with BPD are at higher risk for respiratory exacerbations and hospitalizations due to respiratory infections or other triggers. These episodes can significantly impact their quality of life and overall health.

Health-related quality of life

Physical and functional limitations

Reduced lung function and chronic respiratory symptoms can lead to physical limitations, impacting the ability to participate in normal activities and exercise [6]. This can affect overall physical health and development.

Psychological and social impact

The chronic nature of respiratory symptoms and the associated physical limitations can also have psychological and social implications. Anxiety, depression, and social isolation are not uncommon among BPD survivors, further impacting their quality of life.

Clinical implications

Early identification and monitoring

Early identification of infants at risk for BPD and continuous monitoring of lung function are crucial for managing long-term outcomes [7]. Regular spirometry and clinical assessments can help in early detection of declining lung function and timely intervention.

Interventions and management strategies

Pharmacological treatments: Bronchodilators, inhaled corticosteroids, and other anti-inflammatory medications can be beneficial in managing chronic symptoms and preventing exacerbations. Long-term studies are needed to assess their effectiveness and safety in BPD survivors [8].

Non-pharmacological interventions

Pulmonary rehabilitation, including exercise training and breathing techniques, can improve physical capacity and reduce symptoms. Nutritional support and infection control are also important aspects of comprehensive care.

Need for multidisciplinary care

A multidisciplinary approach, involving pediatricians, pulmonologists, respiratory therapists, and other healthcare professionals, is essential for the holistic management of BPD survivors. Coordination of care can optimize outcomes and enhance the quality of life for these individuals.

Future directions and research

Longitudinal studies

There is a need for long-term longitudinal studies to better understand the natural history of BPD and its long-term pulmonary outcomes. These studies should focus on identifying risk factors, mechanisms of disease progression, and effective interventions [9].

Biomarkers and genetic studies

Research into biomarkers and genetic predispositions can provide insights into the variability in disease presentation and outcomes. Identifying biomarkers for early diagnosis and prognosis can guide personalized treatment strategies.

Novel therapeutic approaches

Exploration of novel therapeutic approaches, including regenerative medicine and targeted therapies, holds promise for improving outcomes in BPD. Advances in understanding the molecular pathways involved in lung injury and repair can lead to the development of new treatments [10].

Results

Pulmonary function

Spirometry and Lung Volumes: Multiple studies have demonstrated that individuals with a history of BPD exhibit persistent reductions in lung function. Specifically, reduced FEV1 and FVC values are common, indicating a combination of obstructive and restrictive lung disease. For instance, a cohort study involving BPD survivors at age 11 revealed that their mean FEV1 was significantly lower than that of their peers born at term .

Diffusion Capacity: Impairment in alveolar-capillary gas exchange is frequently observed, as indicated by reduced DLCO values. This reduction suggests ongoing alveolar simplification and vascular abnormalities into adulthood .

Airway Hyperreactivity: Increased bronchial responsiveness is a hallmark of BPD, with many individuals showing heightened reactivity to methacholine or exercise. This hyperreactivity often leads to increased frequency and severity of wheezing episodes .

Respiratory Symptoms

Chronic Symptoms: Longitudinal studies have reported that BPD survivors frequently experience chronic respiratory symptoms such as wheezing, cough, and dyspnea. These symptoms tend to persist into adolescence and adulthood, significantly impacting daily activities and quality of life .

Exacerbations and Hospitalizations: There is a heightened risk for respiratory exacerbations among BPD survivors, often necessitating hospitalizations. These exacerbations are typically triggered by respiratory infections or environmental pollutants and can lead to a substantial decline in lung function over time .

Health-related quality of life

Physical and Functional Limitations: Due to persistent respiratory symptoms and reduced lung function, individuals with a history of BPD often face significant physical limitations. These limitations affect their ability to engage in physical activities, which can hinder overall growth and development .

Psychological and Social Impact: The chronic nature of respiratory symptoms can lead to psychological distress, including anxiety and depression. Social isolation and difficulties in school or work settings are also common, further diminishing quality of life.

Discussion

Pulmonary function

The observed reductions in lung function among BPD survivors underscore the importance of ongoing pulmonary monitoring. The combination of obstructive and restrictive lung patterns reflects the complex pathophysiology of BPD, where both airway and parenchymal damage contribute to long-term outcomes. Regular spirometry and other pulmonary function tests are essential for early detection of declining lung function and timely intervention.

Respiratory symptoms

Chronic respiratory symptoms in BPD survivors not only reduce quality of life but also increase healthcare utilization. Effective management strategies, including the use of bronchodilators and inhaled corticosteroids, are crucial in mitigating these symptoms. Additionally, early and aggressive treatment of respiratory infections can help prevent exacerbations and further decline in lung function.

Health-related quality of life

The physical limitations and psychological impact observed in BPD survivors highlight the need for a holistic approach to their care. Pulmonary rehabilitation programs that include exercise training can improve physical capacity and reduce symptoms. Psychological support and social interventions are also important to address the broader impacts of the disease.

Clinical implications

Early identification of at-risk infants and continuous monitoring are critical for optimizing long-term outcomes. A multidisciplinary approach involving pediatricians, pulmonologists, respiratory therapists, and other healthcare professionals can provide comprehensive care tailored to the needs of BPD survivors. Coordination of care and personalized treatment plans can enhance the quality of life and health outcomes for these individuals.

Future directions and research

Longitudinal studies are necessary to better understand the natural history of BPD and its long-term pulmonary outcomes. Research into biomarkers and genetic predispositions can provide insights into the variability in disease presentation and outcomes, guiding personalized treatment strategies. Novel therapeutic approaches, such as regenerative medicine and targeted therapies, hold promise for improving outcomes in BPD. Advances in understanding the molecular pathways involved in lung injury and repair can lead to the development of new treatments.

Conclusion

Bronchopulmonary dysplasia remains a significant cause of long-term pulmonary morbidity in premature infants. Understanding the pathophysiological mechanisms and long-term outcomes is crucial for developing effective management strategies. Early identification, continuous monitoring, and a multidisciplinary approach are key to optimizing the health and quality of life of BPD survivors. Future research should focus on longitudinal studies, biomarkers, and novel therapies to further improve outcomes in this vulnerable population.

References

1. Hansen EF, Rasmussen FV,HardtF,KamstrupO (1999)Lung functionand respiratoryhealth of long termfibre-exposedstonewoolfactory workers.AmJRespirCritCare Med160: 466-472.

Indexed at, Google Scholar, Crossref

2. KemanS,JettenM,DouwesJ, Born PJA (1998)Longitudinal changes in inflammatory markers in nasallavageof cotton workers. Relation toedotoxinexposure and lung function changes.IntArchOccupEnvironHlth7: 131-137.

Indexed at, Google Scholar, Crossref

3. Love RG, Smith TA,GurrD,SoutarCA,SearisbbriekDA, et al. (1988)Respiratory and allergic symptoms in wool textile workers.Br JIndMed15: 727-741.

 Indexed at, Google Scholar, Crossref

4. Lin EJ, Chen CH, Lin CC,KuoHT (1995) Respiratory symptoms in reactive dye workers.RespirCritCare Med 151: A421.
5. MengeshaYA,BekeleA (1998)Relative chronic effects of different occupational dusts on respiratory indices and health of workers in three Ethiopian factories.AmJIndMed34: 373-380.

Indexed at, Google Scholar, Crossref

6. Miller WF, Wu N, Johnson R (1956) Miller’s Prediction Quadrant. Anesthesiol 17: 480-493.
7. Nilsson R,NordlinderR,WassU,MedingB,BelinL, et al. (1993)Asthma, rhinitis and dermatitis in workers exposed to reactive dyes.Br JIndMed50: 65-70.

Indexed at, Google Scholar, Crossref

8. OzesmiM,AslanH,HillerdalG,RylanderR,OzesmiC,et al. (1987)Byssinosisin carpet weavers exposed to wool contaminated withendotoxin.Br JIndMed44: 489-483.

Indexed at, Google Scholar, Crossref

9. Park HS, Lee MK, Kim BO, Lee KJ, Roth JM, et al. (1991)Clinical and immunologic evaluations of reactive dye-exposed workers.J AllergyClinImmunol87: 639-649.

Indexed at, Google Scholar, Crossref

10. Parikh JR,MajumdarPK, Shah AR, KasyapSK (1990)Acute and chronic changes in pulmonary functions among textile workers ofAhmedabad.Ind. JIndustMed36: 82-85.

Indexed at, Google Scholar, Crossref