Phenotyping Mouse Pulmonary Function <em>In Vivo</em> with the Lung Diffusing Capacity

Using in vivo measures of aerosol recovery (RC) as a function of breath-hold time (t) (Gebhart et al. J. Appl. Physiol. 51: 465-476, 1981), we estimated the mean diameter (D) of the pulmonary air spaces in subjects diagnosed with chronic obstructive pulmonary disease (COPD) (n = 8) and in subjects with normal pulmonary function (n = 10). For each subject, RC (aerosol expired/aerosol inspired) decreased exponentially with t. Based on a model of the lung as a system of randomly oriented cylindrical tubes, the half time (t1/2) (i.e., the breath-hold time to reach 50% of RC with no breath hold) is proportional to a mean diameter (D) of air spaces filled with aerosol. Subjects with normal pulmonary function had a mean t1/2 = 6.5 +/- 0.8 s, corresponding to a mean D = 0.36 +/- 0.05 mm. On the other hand, subjects with COPD had a mean t1/2 = 12.7 +/- 3.2 s, corresponding to a mean D = 0.70 +/- 0.18 mm [i.e., twice as large (P less than 0.01) as normal subjects]. Furthermore, D correlated significantly with diffusing capacity in the patients with COPD (r = -0.95, P less than 0.001 for D vs. percent predicted diffusing capacity of CO) but not with any other measure of pulmonary function. In contrast, D varied only slightly in normals and did not correlate with any measure of pulmonary function. We conclude that in vivo measures of RC vs. t, in conjunction with other pulmonary function tests, may be a useful tool for identifying actual changes in pulmonary air-space sizes associated with pulmonary disease.

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Digital Clubbing Is Associated with Higher Serum KL-6 Levels and Lower Pulmonary Function in Patients with Interstitial Lung Disease

Canadian Respiratory Journal ◽

10.1155/2018/3640967 ◽

2018 ◽

Vol 2018 ◽

pp. 1-5 ◽

Cited By ~ 2

Author(s):

Kazushige Shiraishi ◽

Torahiko Jinta ◽

Naoki Nishimura ◽

Hiroshi Nakaoka ◽

Ryosuke Tsugitomi ◽

...

Keyword(s):

Interstitial Lung Disease ◽

Pulmonary Function ◽

Lung Disease ◽

Clinical Data ◽

Diffusing Capacity ◽

Partial Pressure Of Oxygen ◽

Digital Clubbing ◽

Common Presentation ◽

Arterial Blood ◽

Lower Oxygen

Background. Although digital clubbing is a common presentation in patients with interstitial lung disease (ILD), little has been reported regarding its role in assessing patients with ILD. This study evaluated patients with ILD for the presence of clubbing and investigated its association with clinical data. Methods. We evaluated patients with ILD who visited the teaching hospital at which the study was conducted, between October 2014 and January 2015. Clubbing, evaluated using a Vernier caliper for individual patients, was defined as a phalangeal depth ratio > 1. We examined the association of clubbing with clinical data. Results. Of 102 patients with ILD, we identified 17 (16.7%) with clubbing. The partial pressure of oxygen in arterial blood was lower (65.2 ± 5.9 mmHg versus 80.2 ± 3.1 mmHg; p=0.03), serum Krebs von den Lugen-6 (KL-6) levels were higher (1495.0 ± 277.4 U/mL versus 839.1 ± 70.2 U/mL; p=0.001), and the percent predicted diffusing capacity of carbon monoxide was lower (50.0 ± 6.0 versus 73.5 ± 3.1; p=0.002) in these patients with clubbing. Conclusions. Patients with clubbing had lower oxygen levels, higher serum KL-6 levels, and lower pulmonary function than those without clubbing.

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Pulmonary function in men after oxygen breathing at 3.0 ATA for 3.5 h

Journal of Applied Physiology ◽

10.1152/jappl.1991.71.3.878 ◽

1991 ◽

Vol 71 (3) ◽

pp. 878-885 ◽

Cited By ~ 24

Author(s):

J. M. Clark ◽

R. M. Jackson ◽

C. J. Lambertsen ◽

R. Gelfand ◽

W. D. Hiller ◽

...

Keyword(s):

Pulmonary Function ◽

Forced Vital Capacity ◽

Vital Capacity ◽

Large Change ◽

Forced Expiratory Volume ◽

Diffusing Capacity ◽

Mild Degree ◽

Oxygen Breathing ◽

Multiple Organs ◽

Expiratory Flow

As a pulmonary component of Predictive Studies V, designed to determine O2 tolerance of multiple organs and systems in humans at 3.0–1.5 ATA, pulmonary function was evaluated at 1.0 ATA in 13 healthy men before and after O2 exposure at 3.0 ATA for 3.5 h. Measurements included flow-volume loops, spirometry, and airway resistance (Raw) (n = 12); CO diffusing capacity (n = 11); closing volumes (n = 6); and air vs. HeO2 forced vital capacity maneuvers (n = 5). Chest discomfort, cough, and dyspnea were experienced during exposure in mild degree by most subjects. Mean forced expiratory volume in 1 s (FEV1) and forced expiratory flow at 25–75% of vital capacity (FEF25–75) were significantly reduced postexposure by 5.9 and 11.8%, respectively, whereas forced vital capacity was not significantly changed. The average difference in maximum midexpiratory flow rates at 50% vital capacity on air and HeO2 was significantly reduced postexposure by 18%. Raw and CO diffusing capacity were not changed postexposure. The relatively large change in FEF25–75 compared with FEV1, the reduction in density dependence of flow, and the normal Raw postexposure are all consistent with flow limitation in peripheral airways as a major cause of the observed reduction in expiratory flow. Postexposure pulmonary function changes in one subject who convulsed at 3.0 h of exposure are compared with corresponding average changes in 12 subjects who did not convulse.

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Effects of irradiation of chest on pulmonary function in man

Journal of Applied Physiology ◽

10.1152/jappl.1961.16.2.331 ◽

1961 ◽

Vol 16 (2) ◽

pp. 331-338 ◽

Cited By ~ 31

Author(s):

C. Emirgil ◽

H. O. Heinemann

Keyword(s):

Pulmonary Function ◽

Total Lung Capacity ◽

Work Of Breathing ◽

Diffusing Capacity ◽

Progressive Reduction ◽

Inspiratory Capacity ◽

Carcinoma Of The Breast ◽

Lung Volumes ◽

Lung Capacity ◽

Arterial Blood

Fifteen patients, free from cardiac and pulmonary disease, but receiving radiotherapy for carcinoma of the breast or carcinoma of the lung, were studied to determine the effect of irradiation on pulmonary function. Lung volumes, the distribution of inspired air, the levels of gases in the arterial blood, the diffusing capacity of the lung, and the mechanics of breathing were measured before and at varying intervals after the completion of radiotherapy. The results showed: early and progressive reduction of inspiratory capacity (IC) and residual volume (RV), decreasing the total lung capacity (TLC) without changing the RV/TLC ratio; unchanged distribution of inspired air; mild hypoxemia at rest; reduced diffusing capacity of the lung for carbon monoxide; and an early and progressive decrease in pulmonary compliance. These observations indicate that irradiation of the chest is complicated by a decrease in lung volumes, an impairment of the diffusing capacity, and an increase in the work of breathing. Submitted on September 6, 1960

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CAUSES OF ISOLATED DIFFUSING CAPACITY OF THE LUNGS FOR CARBON MONOXIDE (DLCO) FROM OUTPATIENT PULMONARY FUNCTION TESTING

CHEST Journal ◽

10.1016/j.chest.2018.08.878 ◽

2018 ◽

Vol 154 (4) ◽

pp. 966A

Author(s):

EKAMJEET RANDHAWA ◽

MICHAEL SHERMAN

Keyword(s):

Carbon Monoxide ◽

Pulmonary Function ◽

Pulmonary Function Testing ◽

Diffusing Capacity ◽

Function Testing

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Effect of a single air dive on pulmonary diffusing capacity in professional divers

Journal of Applied Physiology ◽

10.1152/jappl.1993.74.1.55 ◽

1993 ◽

Vol 74 (1) ◽

pp. 55-61 ◽

Cited By ~ 20

Author(s):

Z. Dujic ◽

D. Eterovic ◽

P. Denoble ◽

G. Krstacic ◽

J. Tocilj ◽

...

Keyword(s):

Pulmonary Function ◽

Time Course ◽

Blood Gases ◽

Diffusing Capacity ◽

Pulmonary Diffusing Capacity ◽

Sequence Of Events ◽

Arterial Blood ◽

Bubble Detection ◽

Venous Gas Embolism ◽

Arterial Po2

The aim of this study was to determine whether venous gas embolism after a single air dive, evaluated using precordial Doppler monitoring, was associated with alterations in spirometry, lung volumes, arterial blood gases, or pulmonary diffusing capacity for carbon monoxide (DLCO). Postdive time course monitoring of pulmonary function was undertaken in 10 professional divers exposed to absolute air pressure of 5.5 bar for 25 min in a dry walk-in chamber. The US Navy decompression table was followed. Venous bubbles were detected by precordial Doppler monitoring. Two types of decompression were used: air and 100% O2 applied for 21 min during decompression stops. Spirometry, flow-volume, and body plethysmography parameters were unchanged after the dive with air decompression (AD) as well as with O2 decompression (OD). A significant reduction in arterial PO2, on average 20 Torr, was found after the dive with AD. DLCO was decreased in all divers 20, 40, 60, and 80 min after diving with AD (P < 0.001), whereas it was not significantly decreased after diving with OD. Maximal DLCO decrease of approximately 15% occurred 20 min postdive. In AD diving, maximum bubble grade for each individual vs. maximum DLCO reduction correlated significantly (r = 0.85, P = 0.002), as well as DLCO vs. arterial PO2 (r = 0.64, P = 0.017). In conclusion, a reduction in pulmonary diffusing capacity is observed in parallel with the appearance of venous bubbles detected by precordial Doppler. We suggest that bubbles cause pulmonary microembolization, triggering a complex sequence of events that remains to be resolved. Measuring DLCO complements Doppler bubble detection in postdiving assessment of pulmonary function.

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Comparative therapeutic efficacy of remdesivir and combination lopinavir, ritonavir, and interferon beta against MERS-CoV

Nature Communications ◽

10.1038/s41467-019-13940-6 ◽

2020 ◽

Vol 11 (1) ◽

Cited By ~ 614

Author(s):

Timothy P. Sheahan ◽

Amy C. Sims ◽

Sarah R. Leist ◽

Alexandra Schäfer ◽

John Won ◽

...

Keyword(s):

Pulmonary Function ◽

Interferon Beta ◽

Lung Pathology ◽

Kingdom Of Saudi Arabia ◽

Viral Loads ◽

Human Infections ◽

Reduce Virus Replication ◽

Severe Lung

AbstractMiddle East respiratory syndrome coronavirus (MERS-CoV) is the causative agent of a severe respiratory disease associated with more than 2468 human infections and over 851 deaths in 27 countries since 2012. There are no approved treatments for MERS-CoV infection although a combination of lopinavir, ritonavir and interferon beta (LPV/RTV-IFNb) is currently being evaluated in humans in the Kingdom of Saudi Arabia. Here, we show that remdesivir (RDV) and IFNb have superior antiviral activity to LPV and RTV in vitro. In mice, both prophylactic and therapeutic RDV improve pulmonary function and reduce lung viral loads and severe lung pathology. In contrast, prophylactic LPV/RTV-IFNb slightly reduces viral loads without impacting other disease parameters. Therapeutic LPV/RTV-IFNb improves pulmonary function but does not reduce virus replication or severe lung pathology. Thus, we provide in vivo evidence of the potential for RDV to treat MERS-CoV infections.

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