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J Appl Physiol 99: 108-113, 2005. First published April 7, 2005; doi:10.1152/japplphysiol.01111.2004
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Developmental changes in airway and tissue mechanics in mice

Elizabeth M. Bozanich,1 Rachel A. Collins,1 Cindy Thamrin,1 Zoltán Hantos,1,2 Peter D. Sly,1 and Debra J. Turner1

1Division of Clinical Sciences, Telethon Institute for Child Health Research and Centre for Child Health Research, University of Western Australia, Perth, Australia; and 2Department of Medical Informatics and Engineering, University of Szeged, Szeged, Hungary

Submitted 4 October 2004 ; accepted in final form 14 March 2005


   ABSTRACT
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 ABSTRACT
METHODS
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 DISCUSSION
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Most studies using mice to model human lung diseases are carried out in adults, although there is emerging interest in the effects of allergen, bacterial, and viral exposure early in life. This study aims to characterize lung function in BALB/c mice from infancy (2 wk) through to adulthood (8 wk). The low-frequency forced oscillation technique was used to obtain impedance data, partitioned into components representing airway resistance, tissue damping, tissue elastance, and hysteresivity (tissue damping/tissue elastance). Measurements were made at end-expiratory pause (transrespiratory system pressure = 2 cmH2O) and during relaxed slow expiration from 20 to 0 cmH2O. Airway resistance decreased with age from 0.63 cmH2O·ml–1·s at 2 wk to 0.24 cmH2O·ml–1·s at 8 wk (P < 0.001). Both tissue damping and tissue elastance decreased with age (P < 0.001) from 2 to 5 wk, then plateaued through to 8 wk (P < 0.001). This pattern was seen both in measurements taken at end-expiratory pause and during expiration. There were no age-related changes seen in hysteresivity when measured at end-expiratory pause, but the pattern of volume dependence did differ with the age of the mice. These changes in respiratory mechanics parallel the reported structural changes of the murine lung from the postnatal period into adulthood.

lung mechanics; mice; age; forced oscillations

MURINE MODELS ARE USED to study many insults to the respiratory and immune system such as viral infections (7), bacterial exposure (21, 24), and allergen exposure (5, 19). There is an increasing body of evidence in humans to suggest that early life exposures are important determinants of immunological development (7, 18) and have long-lasting effects on the respiratory system (6, 7, 23, 29). There is now growing interest in investigating the effects of neonatal exposure to viruses and allergens in the mouse with a view to assessing long-term outcomes (7). Despite the shift of interest to early life exposures, there is no information to date on the effect of lung growth and development on the mechanical properties of airways and respiratory tissues in mice. Such data will be needed to separate developmental changes after early life exposures from normal maturation.

Gomes et al. (11) reported the changes in lung function in rats from early life to adulthood as estimated by a simplified oscillatory technique. The low-frequency forced oscillation technique is an advanced measurement of lung function that applies multiple frequencies simultaneously at the airway opening and enables partitioning of the airway and lung tissue impedances (9, 15, 28). In the present study, we have utilized the low-frequency forced oscillation technique to examine lung function in mice from infancy to adulthood. We have measured respiratory mechanics at end-expiratory pause as well as determining the changes over a wide range of lung volume using a sophisticated system of tracking oscillatory mechanics recently described (14).


   METHODS
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 METHODS
RESULTS
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Animal preparation.   Studies were conducted on BALB/c mice (n = 4–6 mice/group) between 14 days and 8 wk of age. Timed pregnant and specific-age mice were purchased from the Animal Research Centre (Murdoch, Western Australia) for animals to be studied at the exact time points of 2, 3, 4, 5, 6, and 8 wk of age. Gender ratios were evenly distributed in all age groups except the 8-wk group, where only females were studied. Weights ranged from 8.3 ± 0.4 g (mean ± SE) at 2 wk to 20.1 ± 1.0 g in 8-wk-old mice (Table 1). Anesthesia was induced with an intraperitoneal injection of 0.1 ml/10 g body wt mixture containing xylazine (2 mg/ml, Troy Laboratories), ketamine (40 mg/ml, Troy Laboratories), and saline. Two-thirds of the dose was given initially to induce surgical anesthesia. Once an adequate level of anesthesia had been established, a polyethylene cannula (1.0 cm long, inner diameter = 0.086 cm) was inserted into the trachea. Animals were connected to a small animal ventilator (flexiVent, SCIREQ, Montreal, Canada) and ventilated with a tidal volume of 8 ml/kg at a frequency of 450 breaths/min and a positive end-expiratory pressure of 2 cmH2O. The remaining anesthetic was administered when the animal was connected to the ventilator. At the conclusion of the study, mice were killed and inflation fixed with 10% buffered formalin at a pressure of 10 cmH2O. Fixed lung volumes were measured by volume displacement. All aspects of this study conformed to the Australian National Health and Medical Research Council guidelines and were approved by the Institutional Animal Ethics Committee.


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  		Table 1. Influence of age on respiratory mechanics measured at functional residual capacity, set by an end-expiratory pressure of 2 cm H2O for Raw, G, H, and {eta}

 
Measurement of respiratory mechanics.   The mice were allowed to stabilize on the ventilator for 5 min and were then inflated three times to 20 cmH2O to establish a standard volume history. Impedance of the respiratory system (Zrs) was measured using a modification of the forced oscillation technique (9, 26, 28). The oscillatory signals were generated by a loudspeaker in box and delivered to the animal via a wave tube (polyethylene; length = 2 m, inner diameter = 0.116 cm) (16). Ventilation was paused, and the animal were switched to the measurement circuit for the collection of Zrs data. Measurements of Zrs were made at end-expiratory pause, set by a positive end-expiratory pressure of 2 cmH2O, using a pseudorandom oscillatory signal containing 1- to 25-Hz components (28). Eight data epochs (time = 6 s) were collected with 1 min of regular ventilation between each measurement. A four-parameter model (15) was fitted to the Zrs data to obtain airway resistance (Raw) and inertance (Iaw) and the constant-phase parameters of tissue damping (G) and elastance (H). Tissue hysteresivity ({eta}) was calculated as G/H (10). Values of Raw and Iaw were corrected for the resistance and inertance, respectively, of the tracheal cannula. Because most of the inertance resides in the cannula, the values of Iaw were negligible after correction and hence not reported. A representative sample of the impedance spectra is shown for both 2- and 8-wk-old mice, along with the respective model fits, at end-expiratory pause (Fig. 1).



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  		Fig. 1. Representative example of impedance data (mean) obtained at end-expiratory pause (positive end-expiratory pressure = 2 cmH2O) at 2 and 8 wk of age together with the respective model fits.

 
After the measurements at end-expiratory pause, Zrs was measured continuously during slow inflation (time = 20 s) from a transrespiratory pressure (Prs) of 0 to 20 cmH2O and subsequent relaxed expiration (time = 25s) (14). Before each measurement, a 2-s period was allowed for the pressures within the lungs and the equipment to equilibrate. For these measurements, the oscillatory signal consisted of nine non-integer, multiple-frequency components between 4 and 38 Hz. Model fitting was accomplished on successive 0.5-s data segments as previously described (14), providing continuous estimates of Raw, Iaw, G, and H during lung inflation and deflation.

Statistical analysis.   One-way ANOVA was used to compare the effect of age on measurements of Raw, G, H, and {eta} at end-expiratory pause (Prs = 2 cmH2O) and at the beginning (Prs = 20 cmH2O) and end (Prs = 0 cmH2O) of the expiratory maneuver. Differences between groups were assessed with Tukey's multiple comparison test procedure, with Dunn's method employed when equal variance failed on the slow expiration maneuvers. Data are reported as means ± SE. Means were considered significantly different at the P < 0.05 level.


   RESULTS
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Measurements at end expiration.   The influence of age on lung function measured at end-expiratory pause is shown in Table 1. Raw decreased significantly with age (P < 0.001) progressively from 2 wk (0.63 ± 0.08 cmH2O·ml–1·s) to 5 wk (0.25 ± 0.01 cmH2O·ml–1·s), after which Raw differed little from adult (8 wk) values (0.24 ± 0.01 cmH2O·ml–1·s). Coefficients of tissue mechanics G (P < 0.01) and H (P < 0.001) showed a similar pattern of change with age. G decreased from 24.9 ± 1.39 cmH2O/ml at 2 wk to 8.66 ± 0.39 cmH2O/ml at 5 wk of age, after which age values were similar to adult mice (6.98 ± 0.31 cmH2O/ml). Similarly, H fell from 122.0 ± 9.7 cmH2O/ml at 2 wk of age to 42.6 ± 2.9 cmH2O/ml at 5 wk, with little further change to 8 wk (34.7 ± 2.6 cmH2O/ml). There were no significant changes in hysteresivity with age when measured at end-expiratory pause. Normalizing these data for fixed lung displacement volume did not abolish the age dependence (see Table 3).


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  		Table 3. Age dependence of respiratory parameters at end expiratory pause (Prs = 2 cmH2O), normalized to fixed lung volume

 
Respiratory mechanics from 20 to 0 cmH2O.   The dependence of respiratory mechanics on Prs is shown in Figs. 2 (Raw), 3 (G), 4 (H), and 5 ({eta}). Data measured during inspiration and expiration showed the same pattern; thus, for clarity, only the expiratory limbs of the maneuvers are presented. Group mean fitting errors for estimates of Zrs made during relaxed expiration were 6.9 ± 0.4% at 2 wk, 6.5 ± 0.2% at 3 wk, 6.6 ± 0.1% at 4 wk, 7.5 ± 0.8% at 5 wk, 7.3 ± 0.3% at 6 wk, and 8.4 ± 0.2% at 8 wk. There was a progressive downward shift in the Raw-Prs curves with age, with greater spread apparent at a Prs of 0 than at 20 cmH2O (Fig. 2 and Table 2). Curves obtained at 5, 6, and 8 wk were essentially identical. Values of Raw at 0 cmH2O decreased from 1.14 ± 0.11 cmH2O·ml–1·s at 2 wk of age to 0.30 ± 0.04 cmH2O·ml–1·s at 8 wk (a 4-fold decrease). At 20 cmH2O, the differences between mice of different ages were less marked, with the group mean difference between 2- and 8-wk-old mice being 0.18 cmH2O·ml–1·s (Table 2).



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  		Fig. 2. Influence of age on airway resistance (Raw) during relaxed expiration from transrespiratory pressure (Prs) of 20 to 0 cmH2O. Data are means ± SE.

 


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  		Fig. 3. Influence of age on the coefficient of tissue damping (G) during relaxed expiration from Prs of 20 to 0 cmH2O. Data are means ± SE.

 


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  		Fig. 4. Influence of age on the coefficient of tissue elastance (H) during relaxed expiration from raised volume (Prs = 20 cmH2O) to baseline (Prs = 0 cmH2O). Data are means ± SE.

 


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  		Fig. 5. Influence of age on hysteresivity ({eta}) during relaxed expiration from Prs of 20 to 0 cmH2O. Data are means ± SE.

 

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  		Table 2. Age dependence of respiratory parameters at transrespiratory pressures of 0 and 20 cmH2O

 
A downward shift in the G-Prs curves was also seen with increasing age (Fig. 3). There was a clear distinction between mice aged 2 to 4 wk, both in the shape of the curves and the amplitude of G across the inflation range (Table 3). In contrast to the Raw data, the curves obtained in the 5- and 6-wk-old animals are significantly different from the adult (8 wk old) mice (Fig. 3). H-Prs plots shift downward with age (Fig. 4), with clear separation between 2 and 3 wk of age. By 4 wk, the curves are similar to adult (8 wk) mice, and from 5-wk onward they are virtually indistinguishable, except at pressures approaching 20 cmH2O (Table 2).

Whereas there were no age-related changes in {eta} at end expiration, marked differences were seen in the pattern of volume dependence of {eta} for mice of different ages (Fig. 5 and Table 2). These differences are most marked for 2-wk-old mice, with more subtle differences seen in the 3-wk-old group.


   DISCUSSION
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The results of the present study demonstrate the substantial changes that occur in the mechanical parameters of both the airways and the respiratory tissues with growth and development in mice from infancy (2 wk) to adulthood (8 wk). These changes are seen in measurements made at end-expiratory pause and are even more marked when the volume dependence of respiratory mechanics is measured. The major changes occur between 2 and 5 wk of age, after which they change little with further aging up to 8 wk. No age-dependent changes were observed in {eta} when measured at end-expiratory pause. Although all parameters followed the expected pattern of change as lung volume decreased from high lung volume (Prs = 20 cmH2O) to the elastic equilibrium volume of the respiratory system (Prs = 0 cmH2O), marked differences were seen between the youngest and oldest animals.

The only previous study to examine age-related changes in lung mechanics in mice was conducted by Hirai et al. (17); however, the measurements were made on excised lungs and, because the focus of the study was senescence, the youngest age group was 3 mo old. To our knowledge, no studies have examined changes in lung mechanics with growth and development in vivo in the mouse. Several in vitro studies have looked at how lung mechanics change with age in rats (25, 30), and a recent in vivo study investigated maturational changes in respiratory mechanics in rats (11). Gomes et al. (11) measured respiratory mechanics using a forcing function consisting of two frequencies (0.9 and 4.8 Hz) and found resistance and elastance to decrease with age, whereas changes with positive end-expiratory pressure were most evident in the youngest age groups. Although tissue resistance and elastance were estimated from the 0.9-Hz rat Zrs data and the assessment of Raw was based on the 4.8-Hz resistance, the general pattern of their results are consistent with those we now report in mice from multiple-frequency data and model fitting and over a wider range of Prs.

In addition to making the traditional mechanical measurements at end expiration, our study was designed to track changes as the lung was inflated from passive end-expiratory pressure to close to a high lung volume (Prs = 20 cmH2O) and deflated back to baseline (Prs = 0 cmH2O) in vivo. We used forcing functions that covered the frequency range between 1 and 25 and 4 and 38 Hz, respectively, allowing us to partition respiratory mechanics into airway and tissue components. Both data sets provide the opportunity to examine separately the changes occurring in each compartment with age. Mice were studied at key time points in their development. Three weeks is the age of biological weaning; therefore, it was imperative to study mice before, during, and after this key period. Eight weeks is generally accepted to represent adulthood in mice.

Lung structure and composition.   Mice are born without alveoli, and these form rapidly within the first few postnatal weeks (1). The third or fourth postnatal day marks the beginning of distinct changes in lung appearance with primary saccules subdividing into alveoli. This rapid alveolarization continues to day 14, and by day 22 the parenchymal structure is comparable to adult lungs. The development of both alveoli and elastic fiber length is complete by 38 days (20), which is ~5–6 wk of age, corresponding to the age at which the mechanical parameters approached adult values in our study. These milestones in lung development are reflected in the change in lung volume-corrected airway and tissue mechanics (Table 3).

An interesting aspect of the present study is the different messages about lung development that come from the measurements made at end-expiratory pause and during relaxed expiration from high lung volume, especially for measurements of respiratory tissue mechanics. Raw has reached adult levels by 5 wk of age, both at end-expiratory pause and across the range of lung volumes encountered during relaxed expiration (Fig. 2). Both G and H appear to have reached adult levels when measured at end-expiratory pause by 5 wk of age. However, clear differences are seen at high lung volumes, i.e., above 10 cmH2O for G and above 15 cmH2O for H, in both 5- and 6-wk-old animal when compared with adult animals.

The discrepancy in the age-related changes in measurements made at end-expiratory pause and during slow deflation is particularly marked for {eta} describing the coupling between the dissipative and elastic elements of the lung parenchyma (10). When calculated from measurements made at Prs = 2 cmH2O in the present study, there are no differences in {eta} from infancy to adulthood. The approximately constant values of {eta} measured at baseline (Prs = 2 cmH2O) from infancy to adulthood despite substantial lung growth suggest parallel growth of the structures responsible for energy dissipation and the elastic properties of the lung parenchyma. However, substantial age-related differences are seen in the pattern of volume dependence of {eta}, especially in the youngest animals (Fig. 5). We have previously reported the volume dependence of {eta} (22) and suggested that at low lung volumes the mechanical properties of the parenchymal matrix determined {eta}, whereas at high lung volumes the mechanical properties of individual collagen fibers were more important. Interpreted in that light, the age-related pattern of the volume dependence of {eta} suggests that the growth and development of the lungs occurring after the period of rapid alveolarization has been completed involve changes in the tensile strength of the lungs that is provided by the collagen fibers. The reversal in {eta} in the adult mice may reflect the ongoing development of "protective" collagen, inapparent in the separate G and H vs. Prs plots.

It should also be noted that, in the present study, the estimates of G, H, and {eta} reflect the mechanical contribution of the chest wall as well as the pulmonary tissues. This is particularly important in view of the small-amplitude oscillations employed in the present study (the peak-to-peak amplitude did not exceed 2 cmH2O), since the contribution of the chest wall to the total tissue impedance was shown to increase with decreasing amplitude (13). We have previously demonstrated across a similar Prs range in adult mice (28) that the chest wall contributes ~20% to G, and negligibly to H, which results in an ~20% rise in {eta}, in a fairly volume-independent manner. Although these contributions might change with age, being probably even less in the younger mice of softer chest wall, we have not studied them during the development of the respiratory system, because the trauma and the abnormal pattern of lung expansion associated with the open-chest preparation (28) might have led to uncontrollable errors in the assessment of the true contribution of the chest wall to the mechanical properties of the respiratory system.

In the human lung, alveoli are present by 36 wk of gestation with the majority of alveolarization occurring after birth (85–90%) (2, 3, 27). There is conjecture as to when this process ceases (8), but most agree that the majority of alveolar formation occurs in the few weeks before birth up until the first 6–18 mo after birth (2). Changes in lung function with growth and development during the first years of life have been reported in human infants and young children (12, 22, 31). These studies show progressive increases in forced expiratory flows (12, 31) and decreases in Raw (12, 22), G, and H (12) during this time. The changes in respiratory mechanics reported from the present study in mice are compatible with the changes reported with growth in human infants and young children.

No differences were found between sexes in either the mechanical parameters at baseline (end-expiratory pause) or their Prs dependencies; however, the present study was not designed to systematically examine whether gender differences exist in the changes in lung function seen during growth and development. Although this lack of difference may possibly be the result of small study numbers, it has previously been reported that there are no sex differences in growth rate in the early postnatal period (4).

Conclusions.   The present study was conducted to determine how the mechanical properties of the airway and lung parenchyma change with age across a range of transpulmonary pressures between end-expiratory pause (2 cmH2O) and high lung volume (20 cmH2O) in mice. We demonstrated age-related decreases in Raw, G, and H between 2 and 8 wk in BALB/c mice. Raw reached adult levels by 5 wk of age at all Prs, while differences were still present up until 6 wk of age, especially at high lung volumes, for parenchymal mechanics. These age- and volume-related changes need to be understood and taken into account when studies examining the influence of early life exposures on murine models of human lung diseases are designed.

The results of our present study have several implications for the use of mice as models of human lung diseases. Although most studies use adult mice, generally at 8 to 10 wk of age, interest is increasing in studying the effects of early life exposures to a variety of agents, especially viruses and allergens. By 5 wk of age, there is little further change with growth in airway mechanics, whereas changes in the mechanical properties are still occurring until 8 wk of age. This is especially true at lung volumes above end expiration (Prs = 2 cmH2O). Most studies that measure lung function do so at forced residual capacity, either at an end-expiratory pressure set by the ventilator circuit or at Prs of 0 cmH2O. However, in many experimental circumstances, including during methacholine challenge and in the presence of chronic inflammation, changes in lung volume are likely to occur during the study. These protocol-related changes in lung volume may also be more likely when younger mice are studied. Thus it is important that investigators understand both the age-related and lung volume-dependent changes in respiratory mechanics that may complicate their experimental protocol and take these into account in study design.


   GRANTS
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This study was supported by National Health and Medical Research Council Project No. 211912 and Hungarian Scientific Research Fund Grant T42971 [GenBank] .


   FOOTNOTES
 

Address for reprint requests and other correspondence: E. Bozanich, Telethon Institute for Child Health Research, PO Box 855, West Perth, WA 6875, Australia (E-mail: lizb{at}ichr.uwa.edu.au)

The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.


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  1. Amy RW, Bowes D, Burri PH, Haines J, and Thurlbeck WM. Postnatal growth of the mouse lung. J Anat 124: 131–151, 1977.
  2. Burri P. Postnatal development and growth. In: The Lung: Scientific Foundations, edited by Crystal RG, West JB, Weibel ER, and Barnes PJ. Philadelphia, PA: Lippincott-Raven, 1997, p. 1013–1026.
  3. Burri PH. Fetal and postnatal development of the lung. Annu Rev Physiol 46: 617–628, 1984.
  4. Burri PH, Dbaly J, and Weibel ER. The postnatal growth of the rat lung. I. Morphometry. Anat Rec 178: 711–730, 1974.
  5. Chung Y, Cho J, Chang YS, Cho SH, and Kang CY. Preventive and therapeutic effects of oral tolerance in a murine model of asthma. Immunobiology 206: 408–423, 2002.
  6. Colasurdo GN, Hemming VG, Prince GA, Gelfand AS, Loader JE, and Larsen GL. Human respiratory syncytial virus produces prolonged alterations of neural control in airways of developing ferrets. Am J Respir Crit Care Med 157: 1506–1511, 1998.
  7. Culley FJ, Pollott J, and Openshaw PJM. Age at first viral infection determines the pattern of T cell-mediated disease during reinfection in adulthood. J Exp Med 196: 1381–1386, 2002.
  8. Dunhill M. Postnatal growth of the lung. Thorax 17: 29–33, 1962.
  9. Fredberg JJ, Keefe DH, Glass GM, Castile RG, and Frantz ID 3rd. Alveolar pressure nonhomogeneity during small-amplitude high-frequency oscillation. J Appl Physiol 57: 788–800, 1984.
  10. Fredberg JJ and Stamenovic D. On the imperfect elasticity of lung tissue. J Appl Physiol 67: 2408–2419, 1989.
  11. Gomes RF, Shardonofsky F, Eidelman DH, and Bates JH. Respiratory mechanics and lung development in the rat from early age to adulthood. J Appl Physiol 90: 1631–1638, 2001.
  12. Hall GL, Hantos Z, Petak F, Wildhaber JH, Tiller K, Burton PR, and Sly PD. Airway and respiratory tissue mechanics in normal infants. J Appl Physiol 162: 1397–1402, 2000.
  13. Hantos Z, Adamicza A, Govaerts E, and Daroczy B. Mechanical impedances of lungs and chest wall in the cat. J Appl Physiol 73: 427–433, 1992.
  14. Hantos Z, Collins RA, Turner DJ, TZJA, and Sly PD. Tracking of airway and tissue mechanics during TLC maneuvers in mice. J Appl Physiol 95: 1695–1705, 2003.
  15. Hantos Z, Daroczy B, Suki B, Nagy S, and Fredberg JJ. Input impedance and peripheral inhomogeneity of dog lungs. J Appl Physiol 72: 168–178, 1992.
  16. Hantos Z, Petak F, Adamicza A, Daroczy B, and Fredberg JJ. Differential responses of global airway, terminal airway, and tissue impedances to histamine. J Appl Physiol 79: 1440–1448, 1995.
  17. Hirai T, McKeown KA, Gomes RFM, and Bates JHT. Effects of lung volume on lung and chest wall mechanics in rats. J Appl Physiol 86: 16–21, 1999.
  18. Holt PG and Sly PD. Gamma-delta T cells provide a breath of fresh air for asthma research. Nat Med 5: 1127–1128, 1999.
  19. Johnson JR, Wiley RE, Fattouh R, Swirski FK, Gajewska BU, Coyle AJ, Gutierrez-Ramos JC, Ellis R, Inman MD, and Jordana M. Continuous exposure to house dust mite elicits chronic airway inflammation and structural remodeling. Am J Respir Crit Care Med 169: 378–385, 2004.
  20. Kawakami M, Paul JL, and Thurlbeck WM. The effect of age on lung structure in male BALB/cNNia inbred mice. Am J Anat 170: 1–21, 1984.
  21. Kuipers H, Hijdra D, De Vries VC, Hammad H, Prins JB, Coyle AJ, Hoogsteden HC, and Lambrecht BN. Lipopolysaccharide-induced suppression of airway Th2 responses does not require IL-12 production by dendritic cells. J Immunol 171: 3645–3654, 2003.
  22. Lanteri CJ and Sly PD. Changes in respiratory mechanics with age. J Appl Physiol 74: 369–378, 1993.
  23. Larsen GL and Colasurdo GN. Neural control mechanisms within airways: disruption by respiratory syncytial virus. J Pediatr 135: 21–27, 1999.
  24. Miyamoto M, Prause O, Sjostrand M, Laan M, Lotvall J, and Linden A. Endogenous IL-17 as a mediator of neutrophil recruitment caused by endotoxin exposure in mouse airways. J Immunol 170: 4665–4672, 2003.
  25. Nardell EA and Brody JS. Determinants of mechanical properties of rat lung during postnatal development. J Appl Physiol 53: 140–148, 1982.
  26. Petak F, Hall GL, and Sly PD. Repeated measurements of airway and parenchymal mechanics in rats by using low-frequency oscillations. J Appl Physiol 84: 1680–1686, 1998.
  27. Pringle KC. Human fetal lung development and related animal models. Clin Obstet Gynecol 29: 502–513, 1986.
  28. Sly PD, Collins RA, Thamrin C, Turner DJ, and Hantos Z. Volume dependence of airway and tissue impedances in mice. J Appl Physiol 94: 1460–1466, 2003.
  29. Stein RT, Sherrill D, Morgan WJ, Holberg CJ, Halonen M, Taussig LM, Wright AL, and Martinez FD. Respiratory syncytial virus in early life and risk of wheeze and allergy by age 13 years. Lancet 354: 541–545, 1999.
  30. Tanaka R and Ludwig MS. Changes in viscoelastic properties of rat lung parenchymal strips with maturation. J Appl Physiol 87: 2081–2089, 1999.
  31. Tepper RS. Maturation affects the maximal pulmonary response to methacholine in rabbits. Pediatr Pulmonol 16: 48–53, 1993.



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J. L. S. Lofgren, M. R. Mazan, E. P. Ingenito, K. Lascola, M. Seavey, A. Walsh, and A. M. Hoffman
Restrained whole body plethysmography for measure of strain-specific and allergen-induced airway responsiveness in conscious mice
J Appl Physiol, November 1, 2006; 101(5): 1495 - 1505.
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