Effects Of Pulmonary Fibrosis Research Articles

Vinpocetine alleviated alveolar epithelial cells injury in experimental pulmonary fibrosis by targeting PPAR-γ/NLRP3/NF-κB and TGF-β1/Smad2/3 pathways

This study aimed to investigate the potential anti-fibrotic activity of vinpocetine in an experimental model of pulmonary fibrosis by bleomycin and in the MRC-5 cell line. Pulmonary fibrosis was induced in BALB/c mice by oropharyngeal aspiration of a single dose of bleomycin (5 mg/kg). The remaining induced animals received a daily dose of pirfenidone (as a standard anti-fibrotic drug) (300 mg/kg/PO) and vinpocetine (20 mg/kg/PO) on day 7 of the induction till the end of the experiment (day 21). The results of the experiment revealed that vinpocetine managed to alleviate the fibrotic endpoints by statistically improving (P ≤ 0.05) the weight index, histopathological score, reduced expression of fibrotic-related proteins in immune-stained lung sections, as well as fibrotic markers measured in serum samples. It also alleviated tissue levels of oxidative stress and inflammatory and pro-fibrotic mediators significantly elevated in bleomycin-only induced animals (P ≤ 0.05). Vinpocetine managed to express a remarkable attenuating effect in pulmonary fibrosis both in vivo and in vitro either directly by interfering with the classical TGF-β1/Smad2/3 signaling pathway or indirectly by upregulating the expression of Nrf2 enhancing the antioxidant system, activating PPAR-γ and downregulating the NLRP3/NF-κB pathway making it a candidate for further clinical investigation in cases of pulmonary fibrosis.

Interleukin-11 in idiopathic pulmonary fibrosis: predictive value of prognosis and acute exacerbation.

Idiopathic pulmonary fibrosis (IPF) is a fibrotic lung disease with a poor prognosis and unknown aetiology. We have recently clarified the prognostic value of the serum platelet-derived growth factor (PDGF) level in patients with IPF. Interleukin (IL)-11 is a member of the IL-6 family, and in vivo and in vitro studies have suggested that it has profibrotic effects in pulmonary fibrosis. In this study, we investigated the predictive value of the serum IL-11 level in patients with IPF for survival and occurrence of acute exacerbation (AE). This retrospective study included 68 patients with IPF diagnosed according to the 2018 guideline. Serum PDGF levels were measured using the Bio-Plex method and serum IL-11 levels using enzyme-linked immune-sorbent assay. Cytokine production per lung volume was evaluated using the serum cytokine/percent predicted forced vital capacity (%FVC) value. Forty-six patients were male and the median age was 67 years. The serum IL-11/%FVC value was significantly correlated with the percent predicted diffusing capacity of carbon monoxide (ρ=-0.518, P<0.001) and modified Medical Research Council score for shortness of breath (mMRC) (ρ=0.335, P=0.006) by Spearman's rank correlation analysis. Multivariate Cox proportional hazard regression analysis revealed that the serum IL-11/%FVC value was a significant prognostic factor after adjustment for the serum PDGF/%FVC value and other clinical parameters including mMRC and lymphocyte percentage in bronchoalveolar lavage [hazard ratio (HR): 88.540, 95% confidence interval (CI): 1.905-4,115.686, P=0.022]. IL-11/%FVC value was also a significant predictor of AE after adjustment for age and PDGF/%FVC (HR: 1,815.443, 95% CI: 10.49-314,109.219, P=0.004). The serum IL-11/%FVC value was an independent predictor of prognosis and AE occurrence in patients with IPF, and the IL-11 level appeared to show pathophysiologic value in IPF.

β-sitosterol in Various Pathological Conditions: An Update

Abstract: Phytosteroids are biologically active compounds found naturally in herb plasma membranes, with a chemical composition similar to animal plasma membrane cholesterol. It can be found in almost all fats abundant plant’s diets. One of the vital phytosterols is β-sitosterol which has several biological activities. It has been proved in various in-vivo and in-vitro research in which β-sitosterol stabilized several physiological activities like as antioxidant, CNS activity (like anti-alzheimer, anxiolytic and sedative effects, CNS depressant activity), lipid-lowering effects (like nonalcoholic fatty liver disease), antidiabetic, anti-inflammatory and analgesic effects, anticancer and immunomodulatory, protective effects in pulmonary fibrosis, wound healing effects and anti-viral and COVID-19 activity. The experimental research on β-sitosterol shows that it can be used as a nutritional supplement to combat variousexisting diseases. In this review, we are highlighting the most significant pharmacological action of β-sitosterol on the basis of available literature.

Mesenchymal stromal cells attenuate alveolar type 2 cells senescence through regulating NAMPT-mediated NAD metabolism

BackgroundIdiopathic pulmonary fibrosis (IPF) is a chronic and progressive deadly fibrotic lung disease with high prevalence and mortality worldwide. The therapeutic potential of mesenchymal stem cells (MSCs) in pulmonary fibrosis may be attributed to the strong paracrine, anti-inflammatory, anti-apoptosis and immunoregulatory effects. However, the mechanisms underlying the therapeutic effects of MSCs in IPF, especially in terms of alveolar type 2 (AT2) cells senescence, are not well understood. The purpose of this study was to evaluate the role of MSCs in NAD metabolism and senescence of AT2 cells in vitro and in vivo.MethodsMSCs were isolated from human bone marrow. The protective effects of MSCs injection in pulmonary fibrosis were assessed via bleomycin mouse models. The senescence of AT2 cells co-cultured with MSCs was evaluated by SA-β-galactosidase assay, immunofluorescence staining and Western blotting. NAD+ level and NAMPT expression in AT2 cells affected by MSCs were determined in vitro and in vivo. FK866 and NAMPT shRNA vectors were used to determine the role of NAMPT in MSCs inhibiting AT2 cells senescence.ResultsWe proved that MSCs attenuate bleomycin-induced pulmonary fibrosis in mice. Senescence of AT2 cells was alleviated in MSCs-treated pulmonary fibrosis mice and when co-cultured with MSCs in vitro. Mechanistic studies showed that NAD+ and NAMPT levels were rescued in AT2 cells co-cultured with MSCs and MSCs could suppress AT2 cells senescence mainly via suppressing lysosome-mediated NAMPT degradation.ConclusionsMSCs attenuate AT2 cells senescence by upregulating NAMPT expression and NAD+ levels, thus exerting protective effects in pulmonary fibrosis.

Linagliptin ameliorates pulmonary fibrosis in systemic sclerosis mouse model via inhibition of endothelial-to-mesenchymal transition.

Systemic sclerosis (SSc) is a connective tissue disease that often causes pulmonary fibrosis. Dipeptidyl peptidase 4 (DPP4) inhibitor has shown anti-fibrotic properties in various fibrotic diseases. However, only two studies have reported its anti-fibrosis effects in pulmonary fibrosis, and the mechanism is not completely clear. In the present study, we further investigated the protective effects of linagliptin, a highly specific DPP4 inhibitor, on pulmonary fibrosis in SSc mouse model and the potential mechanisms. The results showed that linagliptin ameliorated pulmonary fibrosis in SSc mouse model, as evidenced by improved pathological changes of lung and body weight loss induced by BLM. Linagliptin also reduced BLM-induced oxidative stress, inflammation in lung in vivo. We revealed that linagliptin attenuated BLM-induced endothelial-to-mesenchymal transition (EndMT) in vitro and in vivo. BLM-induced enhanced migration ability of endothelial cells was also alleviated by linagliptin. Moreover, we confirmed that the Akt/mammalian target of rapamycin pathway was involved in BLM-induced EndMT in vivo, which was suppressed by linagliptin. In summary, we further confirmed the therapeutic effects of linagliptin on pulmonary fibrosis in SSc mouse model, which is based on its inhibitory effects on EndMT, oxidative stress, and inflammation.

Alpha-lipoic acid attenuates silica-induced pulmonary fibrosis by improving mitochondrial function via AMPK/PGC1α pathway activation in C57BL/6J mice

Silicosis is characterized by pulmonary interstitial fibrosis that arises as a result of chronic exposure to silica. The few available treatments only delay its progression. As α-lipoic acid (ALA) has been shown to have various beneficial effects, including mitoprotective, antioxidant, and anti-inflammatory effects, we hypothesized that it may exhibit therapeutic effects in pulmonary fibrosis. Therefore, in the present study, we used a murine model of silicosis to investigate whether supplementation with exogenous ALA could attenuate silica-induced pulmonary fibrosis by improving mitochondrial function. ALA was administered to the model mice via continuous intragastric administration for 28 days, and then the antioxidant and mitoprotective effects of ALA were evaluated. The results showed that ALA decreased the production of reactive oxygen species, protected mitochondria from silica-induced dysfunction, and inhibited extracellular matrix deposition. ALA also decreased hyperglycemia and hyperlipidemia. Activation of the mitochondrial AMPK/PGC1α pathway might be responsible for these ALA-mediated anti-fibrotic effects. Exogenous ALA blocked oxidative stress by activating NRF2. Taken together, these findings demonstrate that exogenous ALA effectively prevents the progression of silicosis in a murine model, likely by stimulating mitochondrial biogenesis and endogenous antioxidant responses. Therefore, ALA can potentially delay the progression of silica-induced pulmonary fibrosis.

Effects of Pulmonary Fibrosis and Surface Tension on Alveolar Sac Mechanics in Diffuse Alveolar Damage.

Diffuse alveolar damage (DAD) is a characteristic histopathologic pattern in most cases of acute respiratory distress syndrome and severe viral pneumonia, such as COVID-19. DAD is characterized by an acute phase with edema, hyaline membranes, and inflammation followed by an organizing phase with pulmonary fibrosis and hyperplasia. The degree of pulmonary fibrosis and surface tension is different in the pathological stages of DAD. The effects of pulmonary fibrosis and surface tension on alveolar sac mechanics in DAD are investigated by using the fluid-structure interaction (FSI) method. The human pulmonary alveolus is idealized by a three-dimensional honeycomb-like geometry, with alveolar geometries approximated as closely packed 14-sided polygons. A dynamic compression-relaxation model for surface tension effects is adopted. Compared to a healthy model, DAD models are created by increasing the tissue thickness and decreasing the concentration of the surfactant. The FSI results show that pulmonary fibrosis is more influential than the surface tension on flow rate, volume, P-V loop, and resistance. The lungs of the disease models become stiffer than those of the healthy models. According to the P-V loop results, the surface tension plays a more important role in hysteresis than the material nonlinearity of the lung tissue. Our study demonstrates the differences in air flow and lung function on the alveolar sacs between the healthy and DAD models.

A FRESH LOOK AT OLD GRANULOMAS: 16 YEARS OF HOT TUB LUNG

SESSION TITLE: Medical Student/Resident Occupational and Environmental Lung Disease SESSION TYPE: Med Student/Res Case Rep Postr PRESENTED ON: October 18-21, 2020 INTRODUCTION: Hot Tub Lung is a hypersensitivity pneumonitis provoked by contaminated water exposure. Here we present a case of a man with rapid resolution of 16 years of clinical symptoms and functional disability after removal of his hot tub. CASE PRESENTATION: A 56-year-old man presented for a second opinion for progressive exertional limitation and interstitial lung disease. A surgical lung biopsy performed 16 years previously showed interstitial noncaseating granulomatous inflammation with eosinophils and bronchiolitis obliterans with organizing pneumonia - interpreted as suggestive of hypersensitivity pneumonitis or sarcoidosis. He was told he likely had sarcoidosis and was intermittently treated with steroids. He initially required intermittent oxygen therapy and after 5 years progressed to continuous use at 3 liters per minute. Further history obtained when we saw him was pertinent in that he enjoyed regular use of his hot tub at home. A chest CT scan showed diffuse ground glass opacities without evidence of fibrosis. Sputum cultures were positive for Mycobacterium avium complex (MAC), Mycobacterium fortuitum, Mycobacterium mageritense and Nocardia farcinica. Pathology re-review of his lung biopsy suggested Hot Tub Lung as a potential etiology given well-formed granulomas in a peribronchiolar distribution. On subsequent evaluation 3 months after removing his hot tub, a repeat CT scan showed his bilateral ground glass changes had resolved, sputum cultures were negative and he had no need for supplemental oxygen. His FEV1 in 3 months increased from 1.32 liters (33% predicted) to 2.49 liters (60% predicted) - an 89% improvement. On further discussion 7 months after hot tub removal, our patient felt “let out of prison,” was no longer disabled and was preparing to return to work as an electrician. DISCUSSION: Hot Tub Lung is diagnosed by characteristic findings, including persistent respiratory symptoms like cough and dyspnea, diffuse lung infiltrates on imaging, hot tub exposure and isolation of MAC species on respiratory culture, lung biopsy or hot tub water sample. It is characterized as a hypersensitivity pneumonitis rather than an infectious process as avoidance of antigen exposure is often sufficient to resolve symptoms. To our knowledge, this patient’s long duration of exposure is unique in the literature for Hot Tub Lung. Chronic hypersensitivity pneumonitis is often associated with fibrosis which was not seen here. This suggests that Hot Tub Lung can “smolder” over many years without irreversible change taking place. CONCLUSIONS: Hot Tub Lung should be considered when evaluating a granulomatous lung disorder. This case also highlights the importance of fresh clinicopathologic re-evaluation when diagnoses are in doubt. Reference #1: Mukhopadhyay S, Gal AA. Granulomatous Lung Disease: An Approach to the Differential Diagnosis. Arch Pathol Lab Med. 2010;134:667-690. Reference #2: Hanak V, Kalra S, Aksamit TR, Harman TE, Tazelaar HD, Ryu JH. Hot tub lung: Presenting features and clinical course of 21 patients. Respir Med. 2006;100:610-615. Reference #3: Vourlekis JS, Schwarz MI, Cherniack RM, Curran-Everett D, Cool CD, Tuder RM, et al. The Effect of Pulmonary Fibrosis on Survival in Patients with Hypersensitivity Pneumonitis. Am J Med. 2004;16:662-668. DISCLOSURES: No relevant relationships by Derek Hupp, source=Web Response No relevant relationships by Chris Jensen, source=Web Response No relevant relationships by Jeff Wilson, source=Web Response

Inhibition of miR-182-5p attenuates pulmonary fibrosis via TGF-β/Smad pathway.

Idiopathic pulmonary fibrosis (IPF) is a chronic and progressive lung disease with high morbidity and mortality. miR-182-5p is overexpressed in several fibrosis-related diseases but its effect in pulmonary fibrosis has not been reported yet. To investigate the function of miR-182-5p in pulmonary fibrosis, we established bleomycin (BLM)-induced fibrotic mice model and transforming growth factor-β1 (TGF-β1)-treated human embryonic lung fibroblasts model. In this study, miR-182-5p was highly expressed in pulmonary tissues of BLM-induced fibrotic mice. The content of hydroxyproline and TGF-β1 was decreased by downregulating the expression of miR-182-5p, indicating that fibrosis was alleviated in mice treated with Lentivirus-anti-miR-182-5p.Quantification of fibrosis-related proteins demonstrated that downregulation of miR-182-5p inhibited the expression of profibrotic proteins (fibronectin, α-smooth muscle actin, p-Smad2/p-Smad3) as well as enhanced the level of Smad7. In vitro assays validated that miR-182-5p was induced by TGF-β1 with the function of promoting fibrosis. In dual-luciferase reporter assay, Smad7 was demonstrated to be negatively regulated by miR-182-5p. Moreover, the effect of knocking down miR-182-5p on inhibiting fibrosis was achieved by upregulating the expression of Smad7. Therefore, miR-182-5p can be regarded as a biomarker of IPF and its inhibition may be a promising therapeutic approach in treating IPF.

Effects of mesenchymal stem cells on pulmonary fibrosis

Objective To investigate the effects of mesenchymal stem cells (MSCs) on pulmonary fibrosis under different conditions (different types, different doses and different transplantation times in the same dose). Methods Seventy-two male SD rats were equally divided into 6 groups by random number table method: Group A received intratracheal instillation of NS (0.1 ml). Group B, C, D, E and F received intratracheal instillation of bleomycin (5 mg/kg in 0.1 ml NS). On the 1st day after bleomycin administration, Group A and B received NS (1.0 ml) via the tail vein, while Group C received bone marrow mesenchymal stem cells (BMSCs) 1×106, Group D received umbilical cord blood mesenchymal stem cells (UCB-MSCs) 1×106, Group E received BMSCs 5×105 and Group F received BMSCs 1×107 via the tail vein, respectively. On the 8th day after bleomycin administration, Group E received BMSCs 5×105 again. Half of rats in each group were sacrificed respectively on the 28th and 42nd day after bleomycin administration. The pathologic changes, transforming growth factor-β1 (TGF-β1), hydroxyproline (HYP), matrix metalloproteinase-2 (MMP-2) and tissue inhibitor of metalloproteinase-1 (TIMP-1) of the lung tissues were investigated. Results Alveolar structure was severely in disorder, and massive collagenous fiber was deposited in Group B. In Group B, C, D, E, F and A, the scores of pulmonary fibrosis were decreased in sequence [(3.00±0.00), (2.17±0.75), (1.60±0.89), (1.33±0.52), (1.00±0.00), (0.00±0.00) on the 28th day after bleomycin administration, and (3.00±0.00), (2.40±0.55), (1.75±0.96), (1.50±0.84), (-), (0.00±0.00) on the 42nd day after bleomycin administration], while the levels of TGF-β1, HYP and MMP-2/TIMP-1 were respectively decreased in sequence as above. The levels of TGF-β1, HYP and MMP-2/TIMP-1 were positively associated with pulmonary alveolitis and fibrosis scores respectively (P=0.000). Conclusion MSCs transplantation can suspend the progress of pulmonary fibrosis, and the mechanism may be related to reducing the level of TGF-β1 and improving the imbalance of MMP/TIMP. Choosing UCB-MSCs or multiple transplantation may improve the therapeutic effects of pulmonary fibrosis. Key words: Pulmonary fibrosis; Bleomycin; Bone marrow mesenchymal stem cells; Umbilical cord blood mesenchymal stem cells

Tanshinone IIA ameliorates bleomycin-induced pulmonary fibrosis and inhibits transforming growth factor-beta-β–dependent epithelial to mesenchymal transition

BackgroundEpithelial to mesenchymal transition (EMT) of alveolar epithelial cells occurs in lung fibrotic diseases. Tanshinone ⅡA (Tan ⅡA) has been reported to exert anti-inflammatory effects in pulmonary fibrosis. Nonetheless, whether Tan ⅡA affects lung fibrosis-related EMT remains unknown and requires for further investigations. Materials and methodsA single intratracheal instillation of saline containing bleomycin (BLM; 5 mg/kg body weight) was performed to induce pulmonary fibrosis in Sprague–Dawley rats. Rats receiving an instillation of equivoluminal normal saline served as controls. Then, these rats were given a daily intraperitoneal administration of Tan ⅡA (15 mg/kg body weight) for 28 d before sacrifice. In vitro, recombinant transforming growth factor-beta 1 (TGF-β1; 10 ng/mL) was used to treat human alveolar epithelial A549 cells for 48 h. Tan ⅡA (10 μM) or control DMSO was used to pretreat cells for 2 h before TGF-β1 stimulation. Rat lung tissue samples and A549 cells were then subjected to further assessments. ResultsTan ⅡA was noted to alleviate BLM–induced pulmonary collagen deposition and macrophage infiltration in rats. Epithelial-cadherin expression was decreased after BLM stimulation, whereas α-smooth muscle actin, fibronectin, and vimentin were increased. These expression alterations were partially reversed by Tan ⅡA. Moreover, Tan ⅡA suppressed BLM-induced increases in TGF-β1, phosphorylated Smad-2, and -3 in rats. Additionally, pretreatment of Tan ⅡA inhibited TGF-β1–triggered EMT, reduced collagen Ⅰ production, and blocked TGF-β signal transduction in A549 cells. ConclusionsOur research suggests that Tan ⅡA mitigates BLM–induced pulmonary fibrosis and suppresses TGF-β–dependent EMT of lung alveolar epithelial cells.

Effects of pulmonary fibrosis on the distribution of edema. Morphometric analysis.

We tested the hypothesis that in advanced pulmonary fibrosis, edema is redistributed away from the relatively noncompliant interstitium and predominantly floods alveoli. Severe left lung fibrosis was produced in six dogs with radiation and intratracheal bleomycin and, 24 mo later, hydrostatic edema was induced by infusing 20% body weight Ringer's lactate. Previously we had found, by computed tomography scanning and gravimetry, that similar amounts of water per unit volume accumulated in control and fibrotic lungs; semiquantitative light microscopic grading showed less interstitial and more alveolar edema in the fibrotic lungs. In the present study, we extended these observations with detailed morphometric assessment of volume fractions and absolute volumes of the pulmonary compartments, and we examined the lungs with electron microscopy. We found a twofold rise in the volume fractions of connective tissue and alveolar edema (p < 0.05) and a 50% reduction of air and of interstitial edema in fibrotic lobes (p < 0.05). There was a marked reduction in the absolute volume of edema, paralleling the reduction in lung volume in fibrosis, and minimal gravity-dependent edema gradients in both control and fibrotic lungs. In the latter, evidenced by electron microscopy, the interstitial edema was randomly distributed, whereas in the control lungs, it was found primarily around extra-alveolar vessels and airways, not in the alveolo-capillary septa. We conclude that fibrosis profoundly affects the distribution of edema in the lung.

Effects of pulmonary fibrosis on the distribution of edema. Computed tomographic scanning and morphology.

The pulmonary interstitium acts as an important safety factor against alveolar flooding. To test the hypothesis that in advanced fibrosis, edema is redistributed away from a less compliant interstitium to flood alveoli, we induced severe left lung fibrosis in six dogs with radiation and intratracheal bleomycin. Twenty-four months later, edema was induced by infusing 20% body weight lactated Ringer's solution over 30 min, preceded and followed by computed tomography (CT) scanning. Lower lobes were frozen, and samples were taken for extravascular lung water measurements (Qwl/dQl), regional blood volume, and light microscopic grading of interstitial and alveolar edema. The total volumes of the control and fibrotic lungs were 800 +/- 63 and 45 +/- 10 ml (SE), respectively, indicative of severe fibrosis. Before edema, the fibrotic carinal and basal slices had CT densities 3.5 and 2.2 times greater than respective control slices. After edema, the densities of all control lung slices rose 2.5 times and that of fibrotic carinal and basal slices rose 1.5 times. Edema significantly accentuated the small gravity-dependent gradient in CT density of control lungs, but it had minimal effect on this gradient in fibrotic lungs. The Qwl/dQl for control and fibrotic lower lobes were 8.7 +/- 0.8 and 6.8 +/- 0.7 g H2O/g dry lung, respectively, but the amounts of water per lung volume were similar, and there was no gravity-dependent gradient in Qwl/dQl or in regional blood contents. By light microscopy, we found significantly less interstitial and more alveolar edema in the fibrotic lobes. We conclude that in severe pulmonary fibrosis, similar amounts of water accumulate per lung volume as in controls, and that there is predominant alveolar flooding over interstitial edema. We also conclude that the gravity-dependent gradients in CT densities postedema in the control lungs are not accounted for by edema fluid or congestion, but probably by atelectasis.

Carmustine Toxicity Presenting as a Lobar Infiltrate

Carmustine is a chemotherapeutic agent frequently employed in the treatment of malignant brain tumors. The side effect of pulmonary fibrosis occurs in 20 to 30 percent of patients receiving this drug. Herein we report a case of presumed carmustine-induced pulmonary fibrosis occurring with an unusual lobar distribution.

Effects of pulmonary fibrosis on aerosol deposition in hamsters

Effects of pulmonary fibrosis on aerosol deposition in hamsters

CLINICAL PULMONARY FUNCTION TESTING

Editorials1 August 1959CLINICAL PULMONARY FUNCTION TESTINGBRUCE W. ARMSTRONG, M.D.BRUCE W. ARMSTRONG, M.D.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-51-2-405 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptMany clinicians—doctors who practice medicine and see patients at the bedside rather than those who spend most of their work day in laboratories—frequently think of pulmonary function testing in terms of an elaborate methodology, intricate calculations and an obscure terminology. Although it is perfectly true that many aspects of pulmonary physiology are difficult to understand, there are several tests of pulmonary function with proved, practical value that are basically simple to understand and to use. Equally important, they can be fitted into a schema that unifies the test results into an integrated picture of the patient.Practically, there are three...1 BaldwinCournandRichards EdADW: Pulmonary insufficiency. I. Physiological classification, Medicine 27: 243, 1948. CrossrefMedlineGoogle Scholar2 Macklin C: X-ray studies on bronchial movements, Am. J. Anat. 35: 303, 1925. CrossrefGoogle Scholar3 Motley HL: Pulmonary function in the pneumoconioses, chapter in Clinical cardiopulmonary physiology, edited by Gordon, B., 1957, Grune & Stratton, New York. Google Scholar4 HurtadoFray AWW: Studies of total pulmonary capacity and its subdivisions. II. Correlation with physical and radiological measurements, J. Clin. Investigation 12: 807, 1933. CrossrefMedlineGoogle Scholar5 WhitfieldWaterhouseArnott AGJAWM: The total lung volume and its subdivisions. A study in physiological norms. III. Correlation with other anthropometric data, Brit. J. Social Med. 4: 113, 1950. MedlineGoogle Scholar6 WhitfieldSmithRichardsWaterhouseArnott AGOEDGJAWM: The correlation between the radiological and spirometric appearances and the clinical and spirometric state in emphysema, Quart. J. Med. 20: 247, 1951. MedlineGoogle Scholar7 ShepardCohnCohenArmstrongCarrollDonosoRiley RHJEGBWDGHRL: The maximal diffusing capacity of the lung in chronic obstructive disease of the airways, Am. Rev. Tuberc. and Pul. Dis. 71: 249, 1955. Google Scholar8 CosbyStowellHartwigMayo RSECWRM: Pulmonary function in left ventricular failure, including cardiac asthma, Circulation 15: 492, 1957. CrossrefMedlineGoogle Scholar9 GoughWentworth JJE: The use of thin sections of entire organs in morbid anatomical studies, J. Roy. Micr. Soc. 69: 231, 1949. CrossrefMedlineGoogle Scholar10 CohnCochranPinney JETHC: A comparison of pulmonary physiologic studies with Gough sections of postmortem lungs, Clin. Res. 7: 128, 1959. Google Scholar11 BlumenthalBoren BJHG: Lung structure in three dimensions after inflation and fume fixation, Am. Rev. Tuberc. and Pul. Dis. 79: 764, 1959. Google Scholar12 SheldonOtis MBAB: Effect of adrenalin on resistance to gas flow in the respiratory tract and on the vital capacity of normal and asthmatic subjects, J. Appl. Physiol. 3: 513, 1951. CrossrefMedlineGoogle Scholar13 Dayman H: Mechanics of airflow in health and in emphysema, T. Clin. Investigation 30: 1175, 1951. CrossrefMedlineGoogle Scholar14 Bernstein L: Indications of quantal behavior in the inflation and deflation of rabbit lungs, Second Conference on Research on Emphysema, Aspen, Colorado, June, 1959. Google Scholar15 Bernstein L: A critical discussion of the recorded form of the fast vital capacity record, Thorax 9: 63, 1954. CrossrefMedlineGoogle Scholar16 SteadWellsGaultOganovitch WWHSNLJ: Inaccuracy of the conventional water-filled spirometer for recording rapid breathing, J. Appl. Physiol. 14: 448, 1959. CrossrefMedlineGoogle Scholar17 WellsSteadRossingOganovitch HSWWTDJ: Accuracy of an improved spirometer for recording of fast breathing, J. Appl. Physiol. 14: 451, 1959. CrossrefMedlineGoogle Scholar18 AustrianMcClementRenzettiDonaldRileyCournand RJHADKWRLA: The syndrome of "alveolar-capillary block," Am. J. Med. 11: 667, 1951. CrossrefMedlineGoogle Scholar19 Filley GF: Effects of pulmonary fibrosis on pulmonary function: man, Handbook of respiration, National Academy of Sciences, National Research Council, 1958, W. B. Saunders Company, Philadelphia, p. 268. Google Scholar20 Forster RE: Exchange of gases between alveolar air and pulmonary capillary blood: pulmonary diffusing capacity, Physiol. Rev. 37: 391, 1957. CrossrefMedlineGoogle Scholar21 Bates DV: The measurement of the pulmonary diffusing capacity in the presence of lung disease, J. Clin. Investigation 37: 591, 1958. CrossrefMedlineGoogle Scholar This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAuthors: BRUCE W. ARMSTRONG, M.D.Affiliations: PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 1 August 1959Volume 51, Issue 2Page: 405-412KeywordsPulmonary functionRespiratory physiology ePublished: 1 December 2008 Issue Published: 1 August 1959 PDF downloadLoading ...