Pulmonary diffusing capacity at reduced alveolar volumes in children

Stam, Henk J.; Beek, Agaath van; Grünberg, Katrien; Stijnen, Theo; Tiddens, Harm A.W.M.; Versprille, A.

doi:10.1002/(sici)1099-0496(199602)21:2<84::aid-ppul4>3.0.co;2-p

Cited by 34 publications

(34 citation statements)

References 12 publications

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“…After adjusting for body length, DL CO did not differ significantly for males and females. Although a sex difference in DL CO has been reported for older children when DL CO was adjusted for body length, our study, as well as those in older children (7,8), did not find a sex difference when pulmonary diffusing capacity was adjusted for lung volume. In addition, for our infants and toddlers, DL CO had a higher correlation with alveolar volume than with age or body length.…”

Section: Discussionsupporting

confidence: 75%

“…In older subjects from 8 years of age to adulthood, DL CO and V A increase with somatic growth; however, the ratio (DL CO /V A ) declines in this age range (7,8). These physiologic results are consistent with morphometric data that parenchymal lung growth occurs in this age range primarily by the expansion of the existing number of alveoli, and thus alveolarization is complete by 8 years of age.…”

contrasting

confidence: 91%

“…Our physiologic measurements in infants and toddlers suggest that the ratio of alveolar surface area to alveolar volume remains constant in this very young age group, which is consistent with rapid lung growth early in life occurring by increasing alveolar number rather than increasing alveolar size. In contrast to our findings in infants and toddlers, children between 8 and 18 years of age demonstrate a decline in DL CO /V A with increasing age (7,8). In this older age group, the decline in the ratio of surface area to volume occurs during a period of slower parenchymal growth and it is consistent with morphometric data that there is an expansion of a fixed number of alveoli (16).…”

Section: Discussionmentioning

confidence: 99%

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Growth of the Lung Parenchyma Early in Life

Balinotti¹,

Tiller²,

Llapur³

et al. 2009

Am J Respir Crit Care Med

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Rationale: Early in life, lung growth can occur by alveolarization, an increase in the number of alveoli, as well as expansion. We hypothesized that if lung growth early in life occurred primarily by alveolarization, then the ratio of pulmonary diffusion capacity of carbon monoxide (DL CO ) to alveolar volume (V A ) would remain constant; however, if lung growth occurred primarily by alveolar expansion, then DL CO /V A would decline with increasing age, as observed in older children and adolescents. Objectives: To evaluate the relationship between alveolar volume and pulmonary diffusion capacity early in life. Methods: In 50 sleeping infants and toddlers, with equal number of males and females between the ages of 3 and 23 months, we measured DL CO and V A using single breath-hold maneuvers at elevated lung volumes. Measurements and Main Results: DL CO and V A increased with increasing age and body length. Males had higher DL CO and V A when adjusted for age, but not when adjusted for length. DL CO increased with V A ; there was no gender difference when DL CO was adjusted for V A . The ratio of DL CO /V A remained constant with age and body length. Conclusions: Our results suggest that surface area for diffusion increases proportionally with alveolar volume in the first 2 years of life. Larger DL CO and V A for males than females when adjusted for age, but not when adjusted for length, is primarily related to greater body length in boys. The constant ratio for DL CO /V A in infants and toddlers is consistent with lung growth in this age occurring primarily by the addition of alveoli rather than the expansion of alveoli.Keywords: pulmonary diffusion capacity; alveolar volume; lung development The lung, which provides surface area for gas exchange, begins alveolarization of the lung parenchyma in late gestation; however, the number of alveoli present at birth is estimated to be less than 20% of the number in adults (1-3). In addition, alveolar size of an infant is smaller than the alveolar size of an adult (1-3). Therefore, postnatal growth and development of the lung parenchyma includes increases in number as well as size of alveoli. Lung volume early in life is thought to occur primarily by the addition of alveoli during the rapid phase of somatic growth, and then, following alveolarization of the lung parenchyma, lung volume increases by the expansion of existing alveoli. However, from the limited number of morphometric studies of relatively few autopsied lungs from infants and toddlers, which have used differing morphometric techniques to estimate alveolar number, it remains unclear whether the addition of alveoli is complete by 6 months, 2 to 3 years, or 8 years of age (2, 4-6).In vivo physiologic measurements of alveolar volume (V A ) and pulmonary diffusing capacity for carbon monoxide (DL CO ) can provide a functional assessment of the volume and surface area available for gas exchange, which indirectly reflects the cumulative effects of alveolar number and size. In older subjects from 8 years of age to...

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Section: Discussionsupporting

confidence: 75%

contrasting

confidence: 91%

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Growth of the Lung Parenchyma Early in Life

Balinotti¹,

Tiller²,

Llapur³

et al. 2009

Am J Respir Crit Care Med

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“…Stam et al [7] have recently studied the pre-and postdisease dependence of KCO and TL,CO on VA in a group of young males without previous pulmonary disease, some of whom developed changes in the lungs, accompanied by modest reductions in TL,CO and KCO, when treated with bleomycin for a germ cell tumour. In these males (and in one 11-yr-old female with interstitial lung disease [23]), the absolute change in TL,CO and KCO with change in VA (L) was similar before and after disease developed, supporting their contention that the extent of disease was assessed more correctly, and appeared greater, if values of TL,CO and KCO were compared to reference values for the actual TLC rather than to values for the predicted (predisease) TLC. While this may be justified in the unique circumstances of their study, usually predisease TLC is unknown.…”

Section: Diffuse Alveolar Damagesupporting

confidence: 85%

In defence of the carbon monoxide transfer coefficientK_CO(T_L/V_A)

Hughes

Pride²

2001

Eur Respir J

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In defence of the carbon monoxide transfer coefficient KCO (TL/VA). J.M.B.Hughes, N.B.Pride. #ERS Journals Ltd 2001. ABSTRACT: The carbon monoxide transfer factor (TL,CO) is the product of the two primary measurements during breath-holding, the CO transfer coefficient (KCO) and the alveolar volume (VA). KCO is essentially the rate constant for alveolar CO uptake (Krogh's kCO), and in healthy subjects, increases when VA is reduced by submaximal inflation, or when pulmonary blood flow increases. Recently, new reference values were proposed for clinical use which included the observed VA at full inflation; this was claimed to "eliminate the need for KCO".In this commentary, some mechanisms e.g. respiratory muscle weakness, lung resection, diffuse alveolar damage and airflow obstruction, which decrease or increase total lung capacity (TLC) are reviewed.Even when alveolar structure and function are normal, the change in KCO at a given VA varies according to the underlying pathophysiological mechanism. The advantages and disadvantages of normalizing KCO and TL,CO to predisease predicted TLC or to the patient's actual VA (using lack of expansion or loss of alveolar units models) are considered.Examination of carbon monoxide transfer coefficient and alveolar volume separately provides information on disease pathophysiology which cannot be obtained from their product, the carbon monoxide transfer factor. A few years ago, a paper in the European Respiratory Journal [1] concluded that: ". . . the use of TL/VA (the carbon monoxide (CO) transfer coefficient) cannot be justified on scientific grounds". Apart from one letter of disagreement [2], this view that TL/VA (or KCO) is a redundant and misleading measurement has not been challenged. This is surprising because measurements of TL/VA have continued to be published in respiratory journals.The single breath method for measuring CO uptake by the lung, which is used world-wide, was introduced by Krogh [3] in 1915; this measurement was termed diffusion constant. Subsequently the diffusion constant for CO was renamed the diffusing capacity (DL,CO) or the transfer factor (TL,CO), with the uptake being measured at total lung capacity (TLC). Krogh [3] pointed out that TL,CO was the product of two separate measurements, which potentially varied widely (and independently), the rate constant for CO removal from alveolar gas (called the permeability factor (kCO)) and the alveolar volume (VA).kCO is measured as the exponential decay in fractional concentration of CO over a period of breath-holding (BHT):where CO 0 and CO t are the alveolar CO concentrations at the start and finish of the breath-holding period. The units of kCO are s -1 or min -1 . The total CO transfer of the lung is calculated as:where PB and PH2O are the barometric pressure and the water vapour pressure (at 37 ‡C) which standardize for the driving pressure for CO uptake, i.e.the pressure of CO in the alveoli (PA,CO). VA is the alveolar volume measured at standard temperature and pressure, dry (STPD). In modern usag...

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“…There are also potentially important implications in human studies, specifically those involving children and infants (28). Although the V O 2 /VA in children is similar to that in adults with values ϳ0.10 min Ϫ1 (17,29), which is still considerably smaller than mice (ϳ1.1 min , it is plausible that the effect on the alveolar slope that we have demonstrated in the mouse is also likely to occur to some degree in the neonate and also infant lung.…”

Section: Discussionmentioning

confidence: 99%

The effect of gas exchange on multiple-breath nitrogen washout measures of ventilation inhomogeneity in the mouse

Dharmakumara

Prisk

Royce

et al. 2014

Journal of Applied Physiology

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Dharmakumara M, Prisk GK, Royce SG, Tawhai M, Thompson BR. The effect of gas exchange on multiple-breath nitrogen washout measures of ventilation inhomogeneity in the mouse. J Appl Physiol 117: 1049 -1054, 2014. First published September 11, 2014 doi:10.1152/japplphysiol.00543.2014.-Inert-gas washout measurements using oxygen, in the lungs of small animals, are complicated by the continuous process of oxygen consumption (V O2). The multiplebreath nitrogen washout (MBNW) technique uses the alveolar slope to determine measures of ventilation inhomogeneity in the acinar (S acin) and conducting (S cond) airway regions, as well as overall inhomogeneity, as determined by the lung clearance index (LCI). We hypothesized that measured ventilation inhomogeneity in the mouse lung while it is alive is in fact an artifact due to the high V O2 in proportion to alveolar gas volume (VA), and not ventilation inhomogeneity per se. In seven male C57BL/6 mice, MBNW was performed alive and postmortem to derive measures with and without the effect of gas exchange, respectively. These results were compared with those obtained from an asymmetric multibranch point mathematical model of the mouse lung. There was no statistical difference in S acin and LCI between alive and postmortem results (S acin alive ϭ 0.311 Ϯ 0.043 ml Ϫ1 and Sacin postmortem ϭ 0.338 Ϯ 0.032 ml Ϫ1, LCI alive ϭ 7.0 Ϯ 0.1 and LCI postmortem ϭ 7.0 Ϯ 0.1). However, there was a significant decrease in S cond from 0.086 Ϯ 0.005 ml Ϫ1 alive to 0.006 Ϯ 0.002 ml Ϫ1 postmortem (P Ͻ 0.01). Model simulations replicated these results. Furthermore, in the model, as V O2 increased, so did the alveolar slope. These findings suggests that the MBNW measurement of S cond in the mouse lung is confounded by the effect of gas exchange, a result of the high V O2-to-VA ratio in this small animal, and not due to inhomogeneity within the airways. multiple-breath nitrogen washout; ventilation inhomogeneity; mouse lung; oxygen consumption; alveolar slope THE DISTRIBUTION OF VENTILATION is inhomogeneous, even in the healthy lung. In lung disease, however, ventilation inhomogeneity increases. The degree of inhomogeneity, especially within the small airways, has been demonstrated as an important feature in a number of common respiratory conditions (33, 34), in terms of both pathophysiology and patient-centered outcomes, such as symptoms and disease control (10, 33).One of the most widely used noninvasive methods for measuring ventilation inhomogeneity in humans is the multiple-breath nitrogen washout (MBNW) technique. This test consists of inspiring several consecutive breaths of 100% oxygen (O 2 ) until the nitrogen (N 2 ) concentration in the lungs is reduced to Ͻ2%. Each breath generates an alveolar slope, the evolution of which has been used to measure ventilation inhomogeneity that is a result of convective gas flow (termed S cond ) the site of origin which is thought to be proximal to the so-called diffusion front. The technique also generates a measure that results from inhomogeneity in...

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Pulmonary diffusing capacity at reduced alveolar volumes in children

Cited by 34 publications

References 12 publications

Growth of the Lung Parenchyma Early in Life

Growth of the Lung Parenchyma Early in Life

In defence of the carbon monoxide transfer coefficientK_CO(T_L/V_A)

The effect of gas exchange on multiple-breath nitrogen washout measures of ventilation inhomogeneity in the mouse

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Pulmonary diffusing capacity at reduced alveolar volumes in children

Cited by 34 publications

References 12 publications

Growth of the Lung Parenchyma Early in Life

Growth of the Lung Parenchyma Early in Life

In defence of the carbon monoxide transfer coefficientKCO(TL/VA)

The effect of gas exchange on multiple-breath nitrogen washout measures of ventilation inhomogeneity in the mouse

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Product

Resources

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In defence of the carbon monoxide transfer coefficientK_CO(T_L/V_A)