Down syndrome: Patterns of disturbed lung growth

doi:10.1016/0046-8177(91)90183-P

Human Pathology

Volume 22, Issue 9, September 1991, Pages 919-923

https://doi.org/10.1016/0046-8177(91)90183-P Get rights and content

Abstract

Abnormal pulmonary development characterized by decreased alveolar complexity has been previously reported in patients with Down syndrome. We investigated the state of pulmonary development and found several undescribed patterns of disburbed lung growth. The axial branches of intrasegmental airways were counted in 13 Down syndrome patients; in nine, airway generation was reduced by 25% or more of the predicted number. The radial alveolar counts were evaluated in 11 lungs: five were 143% to 162% above expected (four to above adult values), five were as expected, and one was below expected (82%). No correlation was found between airway number and radial alveolar count. Our finding of the reduction in airway branching in the lungs of patients with Down syndrome suggests interference with development before birth. Disturbances in alveolar multiplication are also found.

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There are more references available in the full text version of this article.

Cited by (57)

Recent Advances in Pediatric Pulmonary Hypertension: Implications for Diagnosis and Treatment
2023, Clinical Therapeutics
Pediatric pulmonary hypertension (PH) is a condition characterized by elevated pulmonary arterial pressure, which has the potential to be life-limiting. The etiology of pediatric PH varies. When compared with adult cohorts, the etiology is often multifactorial, with contributions from prenatal, genetic, and developmental factors. This review aims to provide an up-to-date overview of the causes and classification of pediatric PH, describe current therapeutics in pediatric PH, and discuss upcoming and necessary research in pediatric PH.
PubMed was searched for articles relating to pediatric pulmonary hypertension, with a particular focus on articles published within the past 10 years. Literature was reviewed for pertinent areas related to this topic.
The evaluation and approach to pediatric PH are unique when compared with that of adults, in large part because of the different, often multifactorial, causes of the disease in children. Collaborative registry studies have found that the most common disease causes include developmental lung disease and subsets of pulmonary arterial hypertension, which includes genetic variants and PH associated with congenital heart disease. Treatment with PH-targeted therapies in pediatrics is often guided by extrapolation of adult data, small clinical studies in pediatrics, and/or expert consensus opinion. We review diagnostic considerations and treatment in some of the more common pediatric subpopulations of patients with PH, including developmental lung diseases, congenital heart disease, and trisomy 21.
The care of pediatric patients with PH requires consideration of unique pediatric-specific factors. With significant variability in disease etiology, ongoing efforts are needed to optimize treatment strategies based on disease phenotype and guide evidence-based practices.
Pulmonary Hypertension in Children with Down Syndrome: Results from the Pediatric Pulmonary Hypertension Network Registry
2023, Journal of Pediatrics
Citation Excerpt :
We acknowledge that we may have overestimated the percentage of persistent CHD cases in the registry, given that data pertaining to repair status were limited to the time of enrollment and spontaneous closure of defects was not specifically queried. Growing evidence suggests that children with Down syndrome have insufficient lung development consistent with a lung hypoplasia phenotype.13,14 Bush et al demonstrated that the underdeveloped pulmonary vascular and alveolar phenotype in patients with Down syndrome is similar to that in the lungs of infants with prematurity-associated bronchopulmonary dysplasia, which likely contributes to the increased incidence and severity of pulmonary hypertension.12
To characterize distinct comorbidities, outcomes, and treatment patterns in children with Down syndrome and pulmonary hypertension in a large, multicenter pediatric pulmonary hypertension registry.
We analyzed data from the Pediatric Pulmonary Hypertension Network (PPHNet) Registry, comparing demographic and clinical characteristics of children with Down syndrome and children without Down syndrome. We examined factors associated with pulmonary hypertension resolution and a composite outcome of pulmonary hypertension severity in the cohort with Down syndrome.
Of 1475 pediatric patients with pulmonary hypertension, 158 (11%) had Down syndrome. The median age at diagnosis of pulmonary hypertension in patients with Down syndrome was 0.49 year (IQR, 0.21-1.77 years), similar to that in patients without Down syndrome. There was no difference in rates of cardiac catheterization and prescribed pulmonary hypertension medications in children with Down syndrome and those without Down syndrome. Comorbidities in Down syndrome included congenital heart disease (95%; repaired in 68%), sleep apnea (56%), prematurity (49%), recurrent respiratory exacerbations (35%), gastroesophageal reflux (38%), and aspiration (31%). Pulmonary hypertension resolved in 43% after 3 years, associated with a diagnosis of pulmonary hypertension at age <6 months (54% vs 29%; P = .002) and a pretricuspid shunt (65% vs 38%; P = .02). Five-year transplantation-free survival was 88% (95% CI, 80%-97%). Tracheostomy (hazard ratio [HR], 3.29; 95% CI, 1.61-6.69) and reflux medication use (HR, 2.08; 95% CI, 1.11-3.90) were independently associated with a composite outcome of severe pulmonary hypertension.
Despite high rates of cardiac and respiratory comorbidities that influence the severity of pulmonary hypertension, children with Down syndrome–associated pulmonary hypertension generally have a survival rate similar to that of children with non–Down syndrome–associated pulmonary hypertension. Resolution of pulmonary hypertension is common but reduced in children with complicated respiratory comorbidities.
Developmental and pediatric lung disease
2022, Practical Pulmonary Pathology: A Diagnostic Approach
This chapter provides an overview of the major forms of lung disease affecting neonates, infants, children, and adolescents; where appropriate, it highlights the distinctions from diseases more commonly seen in adults. A standard approach for tissue handling is presented to maximize the diagnostic yield for pediatric lung biopsies and lobectomies. Congenital lung malformations and acquired cystic lesions are discussed, followed by a review of diffuse disorders of lung development, including pulmonary hypoplasia, pulmonary hyperplasia, acinar dysplasia, and congenital alveolar dysplasia. Developmental disorders of the vasculature are also reviewed, including alveolar capillary dysplasia, primary lymphangiectasia, and lymphangiomatosis. Acute and chronic complications of premature birth remain a significant cause of morbidity and mortality in neonates. Pathologic features of hyaline membrane disease, bronchopulmonary dysplasia, and pulmonary interstitial emphysema are summarized. Diffuse lung disease in children includes a variety of patterns of alveolar and interstitial disease including some diseases unique to this age group, such as pulmonary interstitial glycogenosis, neuroendocrine cell hyperplasia of infancy, and the genetic disorders of surfactant metabolism. The differential diagnosis of diffuse lung disease in children also includes entities such as hypersensitivity pneumonitis, eosinophilic pneumonia, aspiration, and obliterative bronchiolitis. These diseases are reviewed briefly and discussed in more detail in other chapters. A practical approach to pathologic diagnosis is emphasized, by way of integration of clinical features, gross pathology, microscopic findings, and use of special studies when necessary.
Pulmonary Cystic Disease and Its Mimics
2020, Surgical Pathology Clinics
Citation Excerpt :
There is a strong association of pleuropulmonary blastoma with DICER1 mutations.18 Occasionally, cases of numerous peripheral cysts, similar to paraseptal emphysema, but often with mild associated fibrosis, have been described in patients with trisomy 21.19 These cysts tend to be subpleural, but can be found in both the apex and the base.
Quality of Pulmonary Function Tests in Participants with Down Syndrome
2019, Archivos de Bronconeumologia
Citation Excerpt :
Down syndrome (DS) is a genetic alteration characterized by trisomy of chromosome 21.1 People with DS have high respiratory morbidity associated with structural, functional and immunological alterations that have substantial impacts in the medium term.2–4 Thus, evaluating the respiratory health of people with chronic respiratory symptoms using standardized, objective tests is desirable.
People with Down syndrome (DS) have high respiratory morbidity, evaluating their respiratory health with standardized, objective tests is desirable. Thus, the objective of this study was to evaluate the technical quality of Pulmonary Function Tests (PFTs) to determine which ones are most suitable for this population.
Participants included children, teenagers and adults with DS, 5 years of age or older (n = 302). The technical quality of the impulse oscillometry system (IOS), forced spirometry, lung-diffusing capacity for carbon monoxide (DL_CO), and 6-min walk test (6MWT) were analyzed by age group. Capnography and pulse oximetry were included in the study. Technical quality was determined on the basis of current international PFTs standards.
Fifty-one percent of participants were males. A total of 184 participants (71%) who completed the IOS fulfilled the quality criteria, while 210 (70%) completed the 6MWT. Performance on forced spirometry and DL_CO was poor. All pulse oximetries and 96% percent heart rates obtained had good quality, but exhaled carbon dioxide (PetCO₂) and respiratory rate (RR) showed deficient repeatability.
IOS appears to be the most reliable instrument for evaluating lung mechanics in individuals with DS.
Las personas con síndrome de Down (SD) tienen una elevada morbilidad respiratoria, por lo que se recomienda evaluar su salud respiratoria con test objetivos estandarizados. El objetivo de este estudio fue evaluar la calidad técnica de los test de función pulmonar (TFP) para determinar cuáles son los más adecuados para este tipo de población.
Entre los participantes se incluyeron niños, adolescentes y adultos con SD y edad ≥5 años (n = 302). Se analizaron por grupos de edad la calidad técnica de la oscilometría de impulso (IOS), la oscilometría forzada, la capacidad pulmonar de difusión del monóxido de carbono (DL_CO) y de la prueba de la marcha de 6 minutos (6MWT). Se incluyeron en el análisis la capnografía y la oximetría de pulso. La calidad técnica se determinó de acuerdo con los estándares internaciones actuales para los TFP.
El 51% de los pacientes eran varones. Un total de 184 participantes (71%) cumplieron los criterios de calidad de la IOS, mientras que 201 (70%) completaron la prueba 6MWT. El desempeño de la espirometría forzada y de la DL_CO fue reducido. Todas las oximetrías de pulso que se obtuvieron, así como el 96% de las frecuencias de pulso presentaron buena calidad. Sin embargo, tanto el dióxido de carbono exhalado (PetCO₂) como la frecuencia respiratoria (FR) presentaron una reproducibilidad deficiente.
La IOS parece ser la herramienta más fiable para la evaluación de la mecánica pulmonar en individuos con SD.
Intrathoracic Cystic Lesions in Neonates and Children
2018, Practical Pulmonary Pathology: A Diagnostic Approach A Volume in the Pattern Recognition Series
This chapter provides an overview of the major forms of lung disease affecting neonates, infants, children, and adolescents; where appropriate, it highlights the distinctions from diseases more commonly seen in adults. A standard approach for tissue handling is presented to maximize the diagnostic yield for pediatric lung biopsies and lobectomies. Congenital lung malformations and acquired cystic lesions are discussed, followed by a review of diffuse disorders of lung development, including pulmonary hypoplasia, pulmonary hyperplasia, acinar dysplasia, and congenital alveolar dysplasia. Developmental disorders of the vasculature are also reviewed, including alveolar capillary dysplasia, primary lymphangiectasia, and lymphangiomatosis. Acute and chronic complications of premature birth remain a significant cause of morbidity and mortality in neonates. Pathologic features of hyaline membrane disease, bronchopulmonary dysplasia, and pulmonary interstitial emphysema are summarized. Diffuse lung disease in children includes a variety of patterns of alveolar and interstitial disease including some diseases unique to this age group, such as pulmonary interstitial glycogenosis, neuroendocrine cell hyperplasia of infancy, and the genetic disorders of surfactant metabolism. The differential diagnosis of diffuse lung disease in children also includes entities such as hypersensitivity pneumonitis, eosinophilic pneumonia, aspiration, and obliterative bronchiolitis. These diseases are reviewed briefly and discussed in more detail in other chapters. A practical approach to pathologic diagnosis is emphasized, by way of integration of clinical features, gross pathology, microscopic findings, and use of special studies when necessary.

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Original contributionDown syndrome: Patterns of disturbed lung growth☆

Abstract

Pulmonary hypoplasia in Down's syndrome

N Engl J Med

Diminished radial count found only postnatally in Down's syndrome

Pediatr Pulmonol

Intrasegmental airway generations and radial alveolar counts in Down's syndrome—Patterns of disturbed lung growth

Am Rev Respir Dis suppl

Postnatal human lung growth

Thorax

Development of the intrasegmental bronchial tree: The pattern of branching and development of cartilage at various stages of intrauterine life

Thorax

Observations on the anatomy of the intrasegmental bronchial tree

Thorax

The number of alveoli in the terminal respiratory unit of man during late intrauterine life and childhood

Arch Dis Child

The radial alveolar count of Emery and Mithal: A reappraisal. 1—Postnatal lung growth

Thorax

The radial alveolar count method of Emery and Mithal: A reappraisal. 2—Intrauterine and early postnatal lungs

Thorax

Original contribution
Down syndrome: Patterns of disturbed lung growth☆