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      Selective dysfunction of the crural diaphragm in patients with chronic restrictive and obstructive lung disease

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          Abstract

          Background:

          Gastroesophageal reflux (GER) is known to be associated with chronic lung diseases. The driving force of GER is the transdiaphragmatic pressure (Pdi) generated mainly by costal and crural diaphragm contraction. The latter also enhances the esophagogastric junction (EGJ) pressure to guard against GER.

          Methods:

          The relationship between Pdi and EGJ pressure was determined using high resolution esophageal manometry in patients with interstitial lung disease (ILD, n = 26), obstructive lung disease (OLD, n- = 24), and healthy subjects ( n = 20).

          Key Results:

          The patient groups did not differ with respect to age, gender, BMI, and pulmonary rehabilitation history. Patients with ILD had significantly higher Pdi but lower EGJ pressures as compared to controls and OLD patients ( p < 0.001). In control subjects, the increase in EGJ pressure at all-time points during inspiration was greater than Pdi. In contrast, the EGJ pressure during inspiration was less than Pdi in 14 patients with ILD and 7 patients with OLD. The drop in EGJ pressure was usually seen after the peak Pdi in ILD group ( p < 0.0001) and before the peak Pdi in OLD group, ( p = 0.08). Nine patients in the ILD group had sliding hiatus hernia, compared to none in control subjects ( p = 0.003) and two patients in the OLD, ( p = 0.04).

          Conclusions and Inferences:

          A higher Pdi and low EGJ pressure, and dissociation between Pdi and EGJ pressure temporal relationship suggests selective dysfunction of the crural diaphragm in patients with chronic lung diseases and may explain the higher prevalence of GERD in ILD as seen in previous studies.

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          Most cited references47

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          The esophagogastric junction.

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            Gastro-oesophageal reflux and gastric aspiration in idiopathic pulmonary fibrosis patients.

            The aim of the study was to characterise gastro-oesophageal reflux (GOR) in idiopathic pulmonary fibrosis (IPF). 40 consecutive IPF patients underwent pulmonary high-resolution computed tomography (HRCT) scan and impedance-pH monitoring while off antisecretory therapy. The presence of pulmonary fibrosis was assessed using validated HRCT scores. Reflux features included distal oesophageal acid exposure, number of acid/weakly acidic reflux episodes and their proximal migration. 40 consecutive patients with interstitial lung disease other than IPF (non-IPF patients) and 50 healthy volunteers were also enrolled. IPF patients had significantly higher (p<0.01) oesophageal acid exposure (median (interquartile range (IQR)) 9.25 (4.7-15.4)% versus 3.3 (1.4-7.4)% versus 0.7 (0.2-4.2)%, number of acid (median (IQR) 45 (23-55) versus 32 (19-44) versus 18 (10-31)), weakly acidic (median (IQR) 34 (19-43) versus 21 (11-33) versus 18 (15-28)) and proximal reflux (median (IQR) 51 (26.5-65.5) versus 20 (9.5-34.5) versus 9 (5-20)) events compared to non-IPF patients and healthy volunteers, respectively. Pulmonary fibrosis HRCT scores correlated well with reflux episodes in both the distal (r(2)=0.567) and proximal (r(2)=0.6323) oesophagus. Patients with IPF had more bile acids and pepsin (p<0.03) in bronchoalveolar lavage fluid (BALF) (62% and 67%, respectively) and saliva (61% and 68%, respectively) than non-IPF patients (25% and 25% in BALF, and 33% and 36%, respectively, in saliva) and controls (0% and 0% in BALF and saliva, respectively). Acid GOR is common in IPF, but weakly acidic GOR may also occur. Patients with IPF had a risk of pulmonary aspiration of gastric contents. Outcome studies with intense antireflux therapy are needed.
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              Contractile properties of the human diaphragm during chronic hyperinflation.

              In patients with chronic obstructive pulmonary disease (COPD) and hyperinflation of the lungs, dysfunction of the diaphragm may contribute to respiratory decompensation. We evaluated the contractile function of the diaphragm in well-nourished patients with stable COPD, using supramaximal, bilateral phrenic-nerve stimulation, which provides information about the strength and inspiratory action of the diaphragm. In eight patients with COPD and five control subjects of similar age, the transdiaphragmatic pressure generated by the twitch response to phrenic-nerve stimulation was recorded at various base-line lung volumes, from functional residual capacity to total lung capacity, and during relaxation and graded voluntary efforts at functional residual capacity (twitch occlusion). At functional residual capacity, the twitch transdiaphragmatic pressure ranged from 10.9 to 26.6 cm of water (1.07 to 2.60 kPa) in the patients and from 19.8 to 37.1 cm of water (1.94 to 3.64 kPa) in the controls, indicating considerable overlap between the two groups. The ratio of esophageal pressure to twitch transdiaphragmatic pressure, an index of the inspiratory action of the diaphragm, was -0.50 +/- 0.05 in the patients, as compared with -0.43 +/- 0.02 in the controls (indicating more efficient inspiratory action in the patients than in the controls). At comparable volumes, the twitch transdiaphragmatic pressure and esophageal-to-transdiaphragmatic pressure ratio were higher in the patients than in normal subjects, indicating that the strength and inspiratory action of the diaphragm in the patients were actually better than in the controls. Twitch occlusion (a measure of the maximal activation of the diaphragm) indicated near-maximal activation in the patients with COPD, and the maximal transdiaphragmatic pressure was 106.9 +/- 13.8 cm of water (10.48 +/- 1.35 kPa). The functioning of the diaphragms of the patients with stable COPD is as good as in normal subjects at the same lung volume. Compensatory phenomena appear to counterbalance the deleterious effects of hyperinflation on the contractility and inspiratory action of the diaphragm in patients with COPD. Our findings cast doubt on the existence of chronic fatigue of the diaphragm in such patients and therefore on the need for therapeutic interventions aimed at improving diaphragm function.
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                Author and article information

                Journal
                9432572
                20191
                Neurogastroenterol Motil
                Neurogastroenterol Motil
                Neurogastroenterology and motility
                1350-1925
                1365-2982
                4 November 2023
                January 2024
                26 October 2023
                01 July 2024
                : 36
                : 1
                : e14699
                Affiliations
                [1 ]Division of Pulmonary Medicine, University of California San Diego, San Diego, California, USA
                [2 ]Division of Gastroenterology, Department of Medicine, University of California San Diego, San Diego, California, USA
                [3 ]Department of Biostatistics and Bioinformatics, University of California San Diego, San Diego, California, USA
                Author notes
                Correspondence Jisha Joshua, Division of Pulmonary Medicine, University of California San Diego, 9444 Medical Center Drive, La Jolla, San Diego, CA 92037, USA. jjoshua@ 123456health.ucsd.edu

                AUTHOR CONTRIBUTIONS

                Jisha Joshua participated in the design of the study, data collection, interpretation of the results, writing, critical revision, and final approval of the manuscript submitted. Chetna Pathak participated in the data collection, interpretation of the results, critical revision and final approval of the manuscript submitted. Ali Zifan participated in the design of the study, creation of manometry software, statistical analysis, interpretation of the results, critical revision and final approval of the manuscript submitted. Ruohui Chen participated in the statistical analysis, interpretation of the results, and final approval of the manuscript submitted. Atul Malhotra participated in the design of the study, critical revision and final approval of the manuscript submitted. Ravinder K Mittal conceived the study idea, participated in the design of the study, data collection, interpretation of the results, writing, critical revision, and final approval of the manuscript submitted.

                Author information
                http://orcid.org/0000-0002-4940-8352
                http://orcid.org/0000-0003-0272-7492
                Article
                NIHMS1941852
                10.1111/nmo.14699
                10842479
                37882102
                aa1aefd1-ce43-4ba7-a0ff-32306cf3324c

                This is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.

                History
                Categories
                Article

                Gastroenterology & Hepatology
                crural diaphragm,esophagogastric junction,gastroesophageal reflux,hiatus hernia,lower esophageal sphincter,transdiaphragmatic pressure gradient

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