Dysanaptic lung growth: an experimental and allometric approach

1983 ◽  
Vol 54 (5) ◽  
pp. 1236-1241 ◽  
Author(s):  
J. P. Mortola

The postnatal development of the mammalian lung, which at birth has only a fraction of the adult number of alveoli, would suggest a mismatch (dysanapsis) of the changes in airway size and lung size with growth. This may have implications on the efficiency of breathing because for any given lung size the dimensions of the airways are the determinant of the amount of dead space (VD) ventilation and of airflow resistance. A comparison of the allometric functions of tracheal dimensions previously published suggests that the tracheal volume, taken as representative of VD, is smaller in newborns than in adults. This difference becomes more apparent when examined per unit of functional residual capacity (VD/FRC). The relatively smaller tracheal volume is the result of both a shorter and narrower trachea in the newborn. This latter difference implies a slightly but significantly higher resistance of the lower airways, as also demonstrated by experimental measurements of peak expiratory flows at a constant driving pressure in rats of different ages. Because the slightly higher resistance of the lower airways is probably compensated by the smaller resistance of the upper airways (J. Appl. Physiol.: Respirat. Environ. Exercise Physiol. 51: 641–645, 1981), it would seem that the structure of the newborn mammalian lung favors the alveolar ventilatory function without a substantial increase of the energetic losses.

Author(s):  
Soula Danopoulos ◽  
Gail H. Deutsch ◽  
Claire Dumortier ◽  
Thomas Jay Mariani ◽  
Denise Al Alam

Down Syndrome (DS) is one of the most prevalent chromosomal abnormalities world-wide, affecting 1 in 700 live births. Although multiple organ systems are affected by the chromosomal defects, respiratory failure and lung disease are the leading causes of morbidity and mortality observed in DS. Manifestations of DS in the respiratory system encompass the entire lung starting from the nasopharynx, trachea/upper airways to the lower airways and alveolar spaces, as well as vascular and lymphatic defects. Most of our knowledge on respiratory illness in persons with DS arises from pediatric studies, however many of these disorders present early in infancy supporting developmental mechanisms. In this review we will focus on the different lung phenotypes in DS, as well as the genetic and molecular pathways that may be contributing to these complications during development.


PEDIATRICS ◽  
1961 ◽  
Vol 27 (4) ◽  
pp. 645-647
Author(s):  
Richard J. Golinko ◽  
Abraham M. Rudolph

PULMONARY function studies in small infants have been limited in the past by failure to develop practical methods for collecting expired gas samples. Adaption of a respiratory valve suitable for use in small subjects with small tidal volumes has been difficult and has led to the use of techniques with the body plethysmograph, contour face mask and large head chamber. The body plethysmograph offers only indirect data and requires considerable prepration before each study. In addition, it has the disadvantage that once the infant is placed in the plethysmograph chamber further manipulations of the infant are not possible. Systems using the contour face mask on head chamber involve a large dead space which may be quite significant when one considers the small volumes dealt with. In order to overcome the problem of large dead space, Cayler et al., similar to others, circulated air across the face of the contour mask. However, because of the dilution effect, differences in the composition of the inspired and expired gases were very small and therefore the chance for error in the calculations was increased. Berglund and Karlberg, and Geubelle et al., while studying functional residual capacity in infants, found that practically all quiet, healthy newborn infants breathe through the nose and can also tolerate the insertion of small tubes in their nostrils for varying periods. On the basis of these observations, a respiratory valve has been designed for insertion directly into the nostrils, permitting collection of total expired air. The valve, especially adapted for use in small infants, offers minimal resistance to respiration and has a dead space of 0.8 ml.


1963 ◽  
Vol 18 (3) ◽  
pp. 519-522 ◽  
Author(s):  
M. C. Hart ◽  
M. M. Orzalesi ◽  
C. D. Cook

The respiratory anatomic dead space has been measured by the single breath nitrogen washout method of Fowler in 73 normal subjects ranging from 4 to 42 years of age. The volume of the anatomic dead space correlated closely with height (Vd (ml) = 7.585 x Ht (cm)2.363 x 10-4·ɣ = .917), but also with body weight, surface area, and functional residual capacity. When compared on the basis of any of these parameters there was no significant difference between the anatomic dead space values for males and females. Comparisons with available data for newborn infants suggest that the value of the anatomic dead space has a relatively constant relation to height from birth to adulthood. Dead space appears to increase more rapidly than weight, surface area, and functional residual capacity during, at least, the early period of somatic growth. Note: (With the Technical Assistance of J. H. Shaw) Submitted on October 25, 1962


1989 ◽  
Vol 67 (4) ◽  
pp. 1418-1421 ◽  
Author(s):  
J. T. McBride

To investigate the role of lung distension in compensatory lung growth, the right lung of each of 21 adult male ferrets was replaced with a silicone rubber balloon filled with mineral oil. Three to thirteen weeks after surgery, the oil was removed through a subcutaneous port. Lung volumes were measured serially until 3–6 wk after balloon deflation. With pneumonectomy the total lung capacity (TLC) decreased to less than 50% of the preoperative value and remained essentially unchanged while the balloon was inflated. At balloon deflation, TLC and vital capacity did not change immediately, whereas functional residual capacity increased by 44%, indicating a change of 2–3 cmH2O in end-expiratory transpulmonary pressure. TLC increased by 10% within 3 days and continued to increase over the subsequent 3–5 wk by a total of 25% over TLC at balloon deflation. There was little difference in this response between animals whose balloons were deflated 3 wk after surgery and those in which deflation was delayed up to 13 wk. After pneumonectomy in the adult ferret, the remaining lung increases in volume in response to an increase in lung distension even weeks or months after surgery. The extent to which this volume increase involves lung tissue growth or depends on previous lung resection is at present unknown. This model may be useful for studies of the mechanisms by which lung distension influences lung volume and compensatory lung growth.


2017 ◽  
Vol 242 ◽  
pp. 12-18 ◽  
Author(s):  
Chris D. Harrison ◽  
Phi Anh Phan ◽  
Cathy Zhang ◽  
Daniel Geer ◽  
Andrew D. Farmery ◽  
...  

1992 ◽  
Vol 24 (4) ◽  
pp. 445-451 ◽  
Author(s):  
Matti Korppi ◽  
Marjaleena Katila ◽  
Raili Kalliokoski ◽  
Maija Leinonen

2017 ◽  
pp. JVI.01322-17 ◽  
Author(s):  
Kok Fei Chan ◽  
Louise A. Carolan ◽  
Julian Druce ◽  
Keith Chappell ◽  
Daniel Watterson ◽  
...  

Small animal models have been used to obtain many insights regarding the pathogenesis and immune responses induced following infection with human respiratory syncytial virus (hRSV). Amongst those described to date, infections in cotton rats, mice, guinea pigs, chinchillas and Syrian hamsters with hRSV strains Long and/or A2 have been well characterised, although clinical isolates have also been examined. Ferrets are also susceptible to hRSV infection but the pathogenesis and immune responses elicited following infection have not been well characterised. Herein, we describe the infection of adult ferrets with hRSV Long or A2 via the intranasal route and characterised virus replication, as well as cytokine induction, in the upper and lower airways. Virus replication and cytokine induction during the acute phase of infection (days 0-15 post-infection) were similar between the two strains and both elicited high levels of F glycoprotein-specific binding and neutralising antibodies following virus clearance (days 16-22 post-infection). Importantly, we demonstrate transmission from experimentally infected donor ferrets to co-housed naïve recipients and have characterised virus replication and cytokine induction in the upper airways of infected contact animals. Together, these studies provide a direct comparison of the pathogenesis of hRSV Long and A2 in ferrets and highlight the potential of this animal model to study serological responses and examine interventions that limit transmission of hRSV.IMPORTANCEFerrets have been widely used to study pathogenesis, immunity and transmission following human influenza virus infections, however far less is known regarding the utility of the ferret model to study hRSV infections. Following intranasal (IN) infection of adult ferrets with the well characterised Long or A2 strains of hRSV, we report virus replication and cytokine induction in the upper and lower airways, as well as the development of virus-specific humoral responses. Importantly, we demonstrate transmission of hRSV from experimentally infected donor ferrets to co-housed naïve recipients. Together, these findings significantly enhance our understanding of the utility of the ferret as a small animal model to investigate aspects of hRSV pathogenesis and immunity.


2020 ◽  
Author(s):  
Susyn Joan Kelly ◽  
Paul Martinsen ◽  
Stanislav Tatkov

Abstract BACKGROUND: Inspired air is heated and humidified in the nose before it reaches lower airways. This mechanism is bypassed during tracheostomy, directly exposing the lower airways to colder and drier air from the environment, which is known to have negative effects on mucociliary transport; however, little is known about how quickly mucociliary transport deteriorates. The purpose of this study was to determine the short-term effect of flowing room air on mucociliary transport in the trachea. In an ovine perfused in vitro tracheal model (N=7) the epithelium was exposed to 25 L/min of flow, heated to lamb body temperature (38 °C) and fully saturated with water vapor as the control, followed by room air (22 °C and 50% relative humidity) for a short duration, until mucociliary transport had visually stopped. Mucus transport velocity (MTV) and cilia beat frequency (CBF), as well as the area of the surface with beating cilia, were continuously measured with video-microscopy.RESULTS: Exposing the tracheal epithelium to air heated to body temperature and fully humidified resulted in stable MTV 9.5 ± 1.1 mm/min and CBF 13.4 ± 0.6 Hz. When exposed to the flow of room air, MTV slowed down to 0.1 ± 0.1 mm/min in 2.0 ± 0.4 seconds followed by a decrease in CBF to 6.7 ± 1.9 Hz, after 2.3 ± 0.8 second. Both MTV and CBF recovered to their initial state when heated and humidified air-flow was re-introduced. CONCLUSIONS: This study demonstrates mucociliary transport can deteriorate within seconds of exposing the tracheal epithelium to flowing room air. The reduction in MTV precedes slowing of CBF. Their relationship is non-linear and a minimum CBF of approximately 6 Hz is required for MTV > 0. Clinically these findings indicate a potential rapid detrimental effect of breathing with non-humidified air via bypassed upper airways.


2020 ◽  
pp. S35-S42
Author(s):  
M. Lucanska ◽  
A. Hajtman ◽  
V. Calkovsky ◽  
P. Kunc ◽  
R. Pecova

Cough is one of the most important defensive reflexes. However, extensive non- productive cough is a harmful mechanism leading to the damage of human airways. Cough is initiated by activation of vagal afferents in the airways. The site of their convergence is particularly the nucleus of the solitary tract (nTS). The second-order neurons terminate in the pons, medulla and spinal cord and there is also the cortical and subcortical control of coughing. Upper airway cough syndrome (UACS) – previously postnasal drip syndrome - is one of the most common causes of chronic cough together with asthma and gastroesophageal reflux. The main mechanisms leading to cough in patients with nasal and sinus diseases are postnasal drip, direct irritation of nasal mucosa, inflammation in the lower airways, upper airway inflammation and the cough reflex sensitization. The cough demonstrated by UACS patients is probably due to hypersensitivity of the upper airways sensory nerve or lower airways sensory nerve, or a combination of both. Further studies are needed to clarify this mechanism.


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