Airway muscle in preterm infants: Changes during development

S, Sward-Comunelli; Mabry, Sherry M; Truog, William E.; Thibeault, Donald W.

doi:10.1016/s0022-3476(97)70241-5

Cited by 60 publications

(34 citation statements)

References 13 publications

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“…The increase in sReff among children with prior BPD, but not in those without, may be associated with increased bronchial smooth muscle and airway narrowing associated with the more prolonged and intense ventilatory support received by these children [34]. These findings of functional impairments are consistent with morphometric data from survivors with BPD [35].…”

Section: Nature Of Underlying Pathophysiologysupporting

confidence: 73%

Nature and severity of lung function abnormalities in extremely pre-term children at 11 years of age

Lum¹,

Kirkby²,

Welsh³

et al. 2010

European Respiratory Journal

154

140

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Advances in neonatal care have resulted in increased survival of children born extremely pre-term (EP). Nevertheless the incidence of bronchopulmonary dysplasia and longterm respiratory morbidity remains high. We investigated the nature of pathophysiological changes at 11 yrs of age to ascertain whether respiratory morbidity in EP children primarily reflects alterations in the lung periphery or more centralised airway function in this population.Spirometry, plethysmography, diffusing capacity, exhaled nitric oxide, multiple-breath washout, skin tests and methacholine challenge were used during laboratory-based assessments in a subgroup of the 1995 EPICure cohort and in controls.Results were obtained in 49 EP and 52 control children. Lung function abnormalities were found in 78% of EP children, with evidence of airway obstruction, ventilation inhomogeneity, gas trapping and airway hyperresponsiveness. Levels of atopy and exhaled nitric oxide were similar between the groups. Prior wheeze was associated with significant reductions in forced flows and volumes. By contrast, abnormalities of the lung periphery appear to be mediated primarily through EP birth per se.The prevalence of lung function abnormalities, which is largely obstructive in nature and likely to have long-term implications, remains high among 11-yr-old children born EP. Spirometry proved an effective means of detecting these persistent abnormalities.

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Section: Nature Of Underlying Pathophysiologysupporting

confidence: 73%

Nature and severity of lung function abnormalities in extremely pre-term children at 11 years of age

Lum¹,

Kirkby²,

Welsh³

et al. 2010

European Respiratory Journal

154

140

View full text Add to dashboard Cite

show abstract

“…In the larger airways, a loss of epithelium from the trachea and main bronchi (28) and an increased area of submucosal glands (18,30) have been reported. Studies that have investigated the smaller airways have shown a greater amount of airway smooth muscle (ASM) (18,19,39,43), increased numbers of goblet cells and altered epithelial cells (18,43). Similar findings have been observed in animal models of ventilatorinduced lung injury following preterm birth.…”

mentioning

confidence: 56%

Persistent bronchiolar remodeling following brief ventilation of the very immature ovine lung

O’Reilly¹,

Hooper

Allison

et al. 2009

American Journal of Physiology-Lung Cellular and Molecular Phys

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We hypothesized that short periods of mechanical ventilation of very immature lungs can induce persistent bronchiolar remodeling that may adversely affect later lung function. Our objectives were to characterize the effects of brief, positive-pressure ventilation per se on the small airways in very immature, surfactant-deficient lungs and to determine whether the effects persist after the cessation of ventilation. Fetal sheep (0.75 of term) were mechanically ventilated in utero with room air (peak inspiratory pressure 40 cmH2O, positive end-expiratory pressure 4 cmH2O, 65 breaths/min) for 6 or 12 h, after which tissues were collected; another group was studied 7 days after 12-h ventilation. Age-matched unventilated fetuses were controls. The mean basement membrane perimeter of airways analyzed was 548.6 Ϯ 8.5 m and was not different between groups. Immediately after ventilation, 21% of airways had epithelial injury; in airways with intact epithelium, there was more airway smooth muscle (ASM) and less collagen, and the epithelium contained more mucin-containing and apoptotic cells and fewer proliferating cells. Seven days after ventilation, epithelial injury was absent but the epithelium was thicker, with greater cell turnover; there were increased amounts of bronchiolar collagen and ASM and fewer alveolar attachments. The increase in ASM was likely due to cellular hypertrophy rather than hyperplasia. We conclude that brief mechanical ventilation of the very immature lung induces remodeling of the bronchiolar epithelium and walls that lasts for at least 7 days; such changes could contribute to later airway dysfunction. epithelium; airway smooth muscle; collagen; proliferation; apoptosis ADVANCES IN PERINATAL CARE have led to improved survival following very preterm birth, with infants born as early as 23-24 wk of gestation now being capable of survival and leading essentially normal lives. However, numerous studies investigating the long-term outcomes of very preterm birth have shown that children (14,17,25,27) and young adults (15) who were born preterm (Ͻ32 wk of gestation) are at an increased risk of having impaired lung function, including reductions in forced expiratory volume in 1 s (FEV 1 ) and forced expiratory flow rates (FEF 25-75% ). Together, these follow-up studies suggest that the small conducting airways may be permanently affected by very preterm birth, especially if these infants subsequently developed bronchopulmonary dysplasia (BPD).Histological studies of the lungs of infants who were mechanically ventilated following preterm birth have shown evidence of damage to the large and small airways. In the larger airways, a loss of epithelium from the trachea and main bronchi (28) and an increased area of submucosal glands (18, 30) have been reported. Studies that have investigated the smaller airways have shown a greater amount of airway smooth muscle (ASM) (18,19,39,43), increased numbers of goblet cells and altered epithelial cells (18,43). Similar findings have been observed in animal models of v...

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“…Changes in lung parenchyma included increased tissue area, edema, atelectasis, reduced secondary septal crest density (26), and disorganized collagen and elastin structure. In the bronchioles, we found epithelial thickening (13,38,47), loss or detachment of the epithelium (34,44), as well as the presence of luminal debris. As in BPD, the injury was heterogeneous, indicative of nonuniform inflation, which is typical of stiff, immature, surfactant-deficient lungs (43).…”

Section: Discussionmentioning

confidence: 83%

Injury and repair in the very immature lung following brief mechanical ventilation

Brew¹,

Hooper

Allison

et al. 2011

American Journal of Physiology-Lung Cellular and Molecular Phys

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Mechanical ventilation (MV) of very premature infants contributes to lung injury and bronchopulmonary dysplasia (BPD), the effects of which can be long-lasting. Little is currently known about the ability of the very immature lung to recover from ventilator-induced lung injury. Our objective was to determine the ability of the injured very immature lung to repair in the absence of continued ventilation and to identify potential mechanisms. At 125 days gestational age (days GA, 0.85 of term), fetal sheep were partially exposed by hysterotomy under anesthesia and aseptic conditions; they were intubated and ventilated for 2 h with an injurious MV protocol and then returned to the uterus to continue development. Necropsy was performed at either 1 day (short-term group, 126 days GA, n ϭ 6) or 15 days (long-term group, 140 days GA, n ϭ 5) after MV; controls were unventilated (n ϭ 7-8). At 1 day after MV, lungs displayed signs of injury, including hemorrhage, disorganized elastin and collagen deposition in the distal airspaces, altered morphology, significantly reduced secondary septal crest density, and decreased airspace. Bronchioles had thickened epithelium with evidence of injury and sloughing. Relative mRNA levels of early response genes (connective tissue growth factor, cysteine-rich 61, and early growth response-1) and proinflammatory cytokines [interleukins (IL)-1␤, IL-6, IL-8, tumor necrosis factor-␣, and transforming growth factor-␤] were not different between groups 1 day after MV. At 15 days after MV, lung structure was normal with no evidence of injury. We conclude that 2 h of MV induces severe injury in the very immature lung and that these lungs have the capacity to repair spontaneously in the absence of further ventilation.ventilator induced lung injury; bronchopulmonary dysplasia; repair; inflammation; preterm birth VERY PRETERM INFANTS OFTEN require mechanical ventilation (MV) due to respiratory insufficiency. However, respiratory support including MV can injure the immature lung and contribute to the development of bronchopulmonary dysplasia (BPD) (10). Structural changes in the lung that are associated with MV and BPD can persist, resulting in deficits in lung function in children (17,19) and young adults (18). Consistent with this, exercise capacity is reduced in children (23, 32) and adolescents (31, 33) who were born very preterm and developed BPD. The structural changes seen in the lungs of infants with BPD include hypercellularity, fewer and larger alveoli, altered vascular growth, and disorganized elastin and collagen deposition (12). In addition, alterations to the small conducting airways have been reported in BPD-affected infants, including increases in airway smooth muscle and the number of goblet cells (47).The causes of BPD remain unclear. While MV is known to be a significant contributor to BPD, other factors are thought to be involved, including infection, use of supplemental oxygen, and impaired nutrition (27). Indeed it has been difficult to identify the role of MV alone, or any othe...

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Airway muscle in preterm infants: Changes during development

Cited by 60 publications

References 13 publications

Nature and severity of lung function abnormalities in extremely pre-term children at 11 years of age

Nature and severity of lung function abnormalities in extremely pre-term children at 11 years of age

Persistent bronchiolar remodeling following brief ventilation of the very immature ovine lung

Injury and repair in the very immature lung following brief mechanical ventilation

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