<?xml version="1.0" encoding="utf8"?>
 <!DOCTYPE article PUBLIC "-//NLM//DTD JATS (Z39.96) Journal Publishing DTD v1.0 20120330//EN" "http://jats.nlm.nih.gov/publishing/1.0/JATS-journalpublishing1.dtd"> <article xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" article-type="research-article" dtd-version="1.0" xml:lang="en">
  <front>
    <journal-meta>
      <journal-id journal-id-type="publisher-id">JCSR</journal-id>
      <journal-title-group>
        <journal-title>Journal of Current Scientific Research</journal-title>
      </journal-title-group>
      <issn pub-type="epub">2766-8681</issn>
      <publisher>
        <publisher-name>Open Access Pub</publisher-name>
        <publisher-loc>United States</publisher-loc>
      </publisher>
    </journal-meta>
    <article-meta>
      <article-id pub-id-type="publisher-id">JCSR-22-4162</article-id>
      <article-id pub-id-type="doi">10.14302/issn.2766-8681.jcsr-22-4162</article-id>
      <article-categories>
        <subj-group>
          <subject>research-article</subject>
        </subj-group>
      </article-categories>
      <title-group>
        <article-title>Can Alveolar-Arterial Oxygen Pressure Difference be used to Diagnose Acute Respiratory Distress Syndrome in Pneumonia Patients?</article-title>
      </title-group>
      <contrib-group>
        <contrib contrib-type="author">
          <name>
            <surname>Ling</surname>
            <given-names>Wang</given-names>
          </name>
          <xref ref-type="aff" rid="idm1842937276">1</xref>
          <xref ref-type="aff" rid="idm1842936340">*</xref>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Wanling</surname>
            <given-names>Wang</given-names>
          </name>
          <xref ref-type="aff" rid="idm1842937276">1</xref>
        </contrib>
      </contrib-group>
      <aff id="idm1842937276">
        <label>1</label>
        <addr-line>Department of Intensive Care Unit, People’s Hospital of Qiandongnan Miao and Dong Autonomous Prefecture, Kaili, Guizhou 556000, China</addr-line>
      </aff>
      <aff id="idm1842936340">
        <label>*</label>
        <addr-line>Corresponding author</addr-line>
      </aff>
      <author-notes>
        <corresp>
    
    Ling Wang, <addr-line>Department of Intensive Care Unit, People’s Hospital of Qiandongnan Miao and Dong Autonomous Prefecture, Kaili, Guizhou 556000, China</addr-line><email>463082910@qq.com</email></corresp>
        <fn fn-type="conflict" id="idm1843182740">
          <p>The authors have declared that no competing interests exist.</p>
        </fn>
      </author-notes>
      <pub-date pub-type="epub" iso-8601-date="2022-05-28">
        <day>28</day>
        <month>05</month>
        <year>2022</year>
      </pub-date>
      <volume>1</volume>
      <issue>4</issue>
      <fpage>20</fpage>
      <lpage>25</lpage>
      <history>
        <date date-type="received">
          <day>13</day>
          <month>04</month>
          <year>2022</year>
        </date>
        <date date-type="accepted">
          <day>26</day>
          <month>05</month>
          <year>2022</year>
        </date>
        <date date-type="online">
          <day>28</day>
          <month>05</month>
          <year>2022</year>
        </date>
      </history>
      <permissions>
        <copyright-statement>© </copyright-statement>
        <copyright-year>2022</copyright-year>
        <copyright-holder>Ling Wang,, et al.</copyright-holder>
        <license xlink:href="http://creativecommons.org/licenses/by/4.0/" xlink:type="simple">
          <license-p>This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.</license-p>
        </license>
      </permissions>
      <self-uri xlink:href="http://openaccesspub.org//jcsr/article/1823">This article is available from http://openaccesspub.org//jcsr/article/1823</self-uri>
      <abstract>
        <p>Alveolar-arterial oxygen pressure difference (P(Aa)O<sub>2</sub>) can reflect pulmonary ability to exchange oxygen; it shows good correlation with the                 oxygenation index (OI), which is important in                      diagnosing acute respiratory distress syndrome (ARDS). This study explored the ability of P(Aa)O<sub>2</sub> in diagnosing ARDS in pneumonia patients. </p>
        <sec id="idm1842786612">
          <title>Methods</title>
          <p>We selected patients with community-acquired pneumonia and sepsis in the intensive care unit (ICU) of the People’s Hospital of Qiandongnan Miao and Dong Autonomous Prefecture; we measured P(Aa)O<sub>2</sub> and the OI under anoxic conditions upon their                admittance to the ICU. We divided the patients into ARDS and non-ARDS groups. We compared the              differences in P(Aa)O<sub>2</sub> and OI; we analyzed the           correlation between P(Aa)O<sub>2</sub> and ARDS. To assess the diagnostic ability of P(Aa)O<sub>2</sub> for ARDS, we drew the receiver operating characteristic (ROC) curve. </p>
        </sec>
        <sec id="idm1842784596">
          <title>Result</title>
          <p>We found that P(Aa)O<sub>2</sub> in the ARDS group was greater than in the non-ARDS group (<italic>t</italic> = 8.875,<italic> P</italic> &lt;0.001); the OI in the ARDS group was smaller than in the non-ARDS group (<italic>t</italic> = –6.956, <italic>P</italic> &lt;0.001). There was a positive correlation between P(Aa)O<sub>2</sub> and ARDS                        (<italic>r</italic> = 0.718, <italic>P</italic> &lt;0.001). The area under the ROC curve for P(Aa)O<sub>2</sub> in the diagnosis of ARDS was 0.931                       (0.873–0.988); the cutoff value was 214.70 mmHg, the sensitivity was 89.50%, and the specificity was 85.00%. </p>
        </sec>
        <sec id="idm1842782652">
          <title>Conclusion</title>
          <p>We conclude that P(Aa)O<sub>2</sub> is a good reference index in diagnosing ARDS.</p>
        </sec>
      </abstract>
      <kwd-group>
        <kwd>alveolar-arterial oxygen pressure difference</kwd>
        <kwd>community-acquired pneumonia</kwd>
        <kwd>diagnosis</kwd>
        <kwd>sepsis</kwd>
        <kwd>acute respiratory distress syndrome</kwd>
        <kwd>oxygenation index</kwd>
      </kwd-group>
      <counts>
        <fig-count count="6"/>
        <table-count count="2"/>
        <page-count count="8"/>
      </counts>
    </article-meta>
  </front>
  <body>
    <sec id="idm1842789204" sec-type="intro">
      <title>Introduction</title>
      <p>Pneumonia is a common disease of the                   respiratory system and has a high incidence. If diffuse pulmonary lesions and hypoxemia develop, acute                respiratory distress syndrome (ARDS) may result<xref ref-type="bibr" rid="ridm1841589084">1</xref>. ARDS patients frequently need to undergo intensive care unit (ICU) treatment owing to that dangerous,                   complex condition <xref ref-type="bibr" rid="ridm1841658244">2</xref>. Currently, there is no specific                treatment for ARDS; the mortality rate can attain             40%–50% <xref ref-type="bibr" rid="ridm1841668756">3</xref><xref ref-type="bibr" rid="ridm1841445740">4</xref><xref ref-type="bibr" rid="ridm1841449124">5</xref>. Early diagnosis and active, effective                 intervention measures are important toward improving the success rate. According to the Berlin definition, the oxygenation index (OI) constitutes an important indicator for the clear diagnosis and risk stratification of ARDS<xref ref-type="bibr" rid="ridm1841433340">6</xref>; the OI can be used as a standard for clinical diagnosis and   developing a guide treatment plan. Alveolar-arterial                 oxygen pressure difference (P(Aa)O<sub>2</sub>) is the difference  between alveolar and arterial oxygen partial pressure; it can be used to accurately assess pulmonary ventilation and pulmonary oxygen uptake <xref ref-type="bibr" rid="ridm1841430676">7</xref>. ARDS presents the      pathological features of diffuse pulmonary inflammation and dysfunctional oxygen exchange. Both P(Aa)O<sub>2</sub> and OI can reflect the state of pulmonary oxygen exchange. To provide a reference for clinical practice, the present study evaluated the effectiveness of P(Aa)O<sub>2</sub> in diagnosing ARDS in pneumonia patients.</p>
    </sec>
    <sec id="idm1842788844" sec-type="materials">
      <title>Material and Methods</title>
      <sec id="idm1842787548">
        <title>Subjects </title>
        <p>We selected the study participants among 206 patients with community-acquired pneumonia (CAP) and sepsis who were admitted to the ICU of the People’s                 Hospital of Qiandongnan Miao and Dong Autonomous   Prefecture from January 1, 2016 to April 10, 2022. We  excluded 22 patients with cardiac insufficiency, 18 with lung malignancy, and 10 with chest trauma; thus, 156            patients were enrolled in this study. They comprised 108 men and 48 women, aged 56–80 years (mean 69.74 ± 6.72 years); there were 76 cases of ARDS and 80 of non-ARDS.</p>
      </sec>
      <sec id="idm1842778252">
        <title>CAP Diagnostic Criteria</title>
        <p>The criteria were as follows: A, community onset; B, pneumonia-related clinical manifestations-(1) recent coughing, expectoration, or aggravation of original                 respiratory disease symptoms; (2) fever; (3) signs of              pulmonary consolidation or audible moist wheezing; (4) peripheral blood leukocytes &gt;10 × 10<sup>9</sup>/L or &lt;4 × 10<sup>9</sup>/L; C, chest imaging showed new patchy infiltrates, consolidation of the lobe or segment, and ground-glass or interstitial changes. We were able to confirm the clinical diagnosis of CAP if we found any of criteria A–C and had excluded the following: pulmonary tuberculosis; pulmonary tumor; noninfectious pulmonary interstitial disease; pulmonary edema; atelectasis; pulmonary embolism; pulmonary                eosinophilic infiltration; and pulmonary vasculitis<xref ref-type="bibr" rid="ridm1841434852">8</xref>.</p>
      </sec>
      <sec id="idm1842776668">
        <title>Sepsis Diagnostic Criteria</title>
        <p>We followed the definition and diagnostic criteria of sepsis 3.0 jointly issued by the American Society of   Critical Care Medicine and European Society of Critical Care Medicine<xref ref-type="bibr" rid="ridm1841411404">9</xref>.</p>
      </sec>
      <sec id="idm1842778684">
        <title>ARDS Diagnostic Criteria</title>
        <p>The criteria were as follows: A, onset time within 1 week after known predisposing factors, new respiratory symptoms, or exacerbation of original symptoms; B,               increased opacity of both lungs in chest imaging that could not be satisfactorily explained by pleural effusion,                  atelectasis, or nodules; C, pulmonary edema with                    respiratory failure that could not be accounted for by              cardiac failure or fluid overload; D, hypoxemia with an OI ≤300 mmHg<xref ref-type="bibr" rid="ridm1841433340">6</xref>.</p>
      </sec>
      <sec id="idm1842774292">
        <title>Treatment </title>
        <p>We treated all patients with antibiotics                         according to standard practice; they received                         expectorants, anti-asthmatics, nutritional support, and mechanical ventilation as necessary. We undertook the timing and mode of ARDS mechanical ventilation                   according to guidelines for such ventilation <xref ref-type="bibr" rid="ridm1841433340">6</xref>,<xref ref-type="bibr" rid="ridm1841434852">8</xref>.</p>
      </sec>
      <sec id="idm1842775588">
        <title>Exclusion Criteria</title>
        <p>We excluded patients with complicated cardiac insufficiency, pulmonary poisoning, lung malignancy, and pulmonary trauma. We also excluded patients with                  incomplete data.</p>
      </sec>
      <sec id="idm1842775876">
        <title>Measurements</title>
        <p>Patients were assessed for ARDS within 24 hours of ICU admission; we divided them into ARDS and                     non-ARDS groups. After patient admission to hospital, 2 ml of arterial blood was withdrawn under anoxic               conditions; we immediately undertook blood gas analysis (REDU ABL800 blood gas analyzer, Denmark, according to manufacturer instructions) to determine P(Aa)O<sub>2</sub> and OI. We compared the two groups with respect to gender, age, and P(Aa)O<sub>2</sub> and OI levels. We examined the correlation between P(Aa)O<sub>2</sub> and ARDS. To analyze the diagnostic ability of P(Aa)O<sub>2</sub> for ARDS, we drew the receiver                    operating characteristic (ROC) curve.</p>
      </sec>
    </sec>
    <sec id="idm1842774076">
      <title>Statistical Analysis</title>
      <p>We employed SPSS 24.0 statistical software for data analysis. To test the normality of the measurement data, we applied the Kolmogorov-Smirnov method. We expressed the measurement data of normal distribution as mean ± standard deviation. We applied the following: an independent-sample <italic>t </italic>test for group comparison; the <italic>χ</italic><sup>2</sup> test for count data; the Pearson correlation analysis for correlation between P(Aa)O<sub>2</sub> and ARDS; <italic>r</italic> for expression; and ROC curve analysis to assess the diagnostic ability of P(Aa)O<sub>2 </sub>for ARDS. We considered a <italic>P</italic> value below 0.05                statistically significant.</p>
    </sec>
    <sec id="idm1842771772" sec-type="results">
      <title>Results</title>
      <p>We observed no significant differences in gender, age, P(Aa)O<sub>2</sub>, and OI between the two groups (<italic>χ</italic><sup>2</sup>/<italic>t </italic>= 0.681, 0.461; <italic>P &gt;</italic>0.05). P(Aa)O<sub>2</sub> in the ARDS group was greater than in the non-ARDS group (<italic>t </italic>= 8.875; <italic>P &lt;</italic>0.001; OI in the ARDS group was smaller than in the non-ARDS group                (<italic>t</italic> = –6.956;<italic> P &lt;</italic>0.001. The differences were statistically significant (<xref ref-type="table" rid="idm1842641388">Table 1</xref>). Our ROC curve analysis showed that the area under the curve for the diagnostic ability of P(Aa)O<sub>2</sub> for ARDS was 0.931 (0.873–0.988). The cutoff value was 214.70 mmHg, the sensitivity 89.50%, and the                 specificity 85.00% (<xref ref-type="fig" rid="idm1842607332">Figure 1</xref>).</p>
      <table-wrap id="idm1842641388">
        <label>Table 1.</label>
        <caption>
          <title> Gender, age, P(Aa)O2, and OI in the ARDS and non-ARDS groups</title>
        </caption>
        <table rules="all" frame="box">
          <tbody>
            <tr>
              <td>group</td>
              <td>Number of cases（n）</td>
              <td>Male/Female（n/n）</td>
              <td>Age(year)</td>
              <td>P(A-a)O<sub>2</sub> (mmHg)</td>
              <td>OI(mmHg)</td>
            </tr>
            <tr>
              <td>ARDS group</td>
              <td>76</td>
              <td>56/20</td>
              <td>70.11±7.32</td>
              <td>314.28±108.37<sup>＊</sup></td>
              <td>140.53±68.79<sup>＊</sup></td>
            </tr>
            <tr>
              <td>non-ARDS group</td>
              <td>80</td>
              <td>52/28</td>
              <td>69.40±6.17</td>
              <td>132.55±66.1</td>
              <td>342.58±60.53</td>
            </tr>
            <tr>
              <td><italic>χ</italic><xref ref-type="bibr" rid="ridm1841658244">2</xref><italic>/</italic><italic>t </italic>value</td>
              <td> </td>
              <td>0.681</td>
              <td>0.461</td>
              <td>8.875</td>
              <td>-6.965</td>
            </tr>
            <tr>
              <td><italic>P </italic>value</td>
              <td> </td>
              <td>0.280</td>
              <td>0.646</td>
              <td>0.000</td>
              <td>0.000</td>
            </tr>
          </tbody>
        </table>
        <table-wrap-foot>
          <fn id="idm1842743468">
            <label/>
            <p>Note: <sup>＊</sup>compared with the non-ARDS group, P＜0.01</p>
          </fn>
        </table-wrap-foot>
      </table-wrap>
      <fig id="idm1842607332">
        <label>Figure 1.</label>
        <caption>
          <title> ROC curve for the diagnostic ability of P(Aa)O2 for ARDS</title>
        </caption>
        <graphic xlink:href="images/image1.jpg" mime-subtype="jpg"/>
      </fig>
    </sec>
    <sec id="idm1842743108" sec-type="discussion">
      <title>Discussion</title>
      <p>Serious lung inflammation in sepsis patients                 may directly lead to pulmonary injury. It can arise as an inflammatory response to pulmonary capillary endothelial cells and alveolar epithelial cells damaged by a significant increase in alveolar capillary wall permeability; it may spread extensively in the lung and produce pulmonary interstitial edema <xref ref-type="bibr" rid="ridm1841407588">10</xref><xref ref-type="bibr" rid="ridm1841404636">11</xref><xref ref-type="bibr" rid="ridm1841399940">12</xref><xref ref-type="bibr" rid="ridm1841394108">13</xref><xref ref-type="bibr" rid="ridm1841393172">14</xref>. The result can be impaired oxygen exchange, lung compliance, and significantly reduced              pulmonary function <xref ref-type="bibr" rid="ridm1841387196">15</xref>. ARDS is clinically characterized by stubborn hypoxemia. ARDS is a common cause of death among ICU patients with severe pulmonary infection; the fatality rate is high  and treatment is difficult<xref ref-type="bibr" rid="ridm1841402460">16</xref>.                   Reportedly, most patients who recover suffer                          severe sequelae <xref ref-type="bibr" rid="ridm1841379628">17</xref>,<xref ref-type="bibr" rid="ridm1841375812">18</xref>, which makes it difficult for                     them to lead normal lives. For ARDS patients with severe pulmonary infection, timely effective preventive measures, appropriate determination of ARDS status, and well-timed effective intervention are key to successful treatment <xref ref-type="bibr" rid="ridm1841668756">3</xref>. ARDS patients have an imbalance between ventilation and blood flow ratio, resulting in a decreased respiratory quotient; simultaneously, there is reduced arterial oxygen partial pressure, leading to an increase in P(Aa)O<sub>2 </sub><xref ref-type="bibr" rid="ridm1841373508">19</xref>,<xref ref-type="bibr" rid="ridm1841370484">20</xref>. Studies have shown that P(Aa)O<sub>2</sub> can                   accurately reflect ARDS patients’ intrapulmonary shunt and diffuse dysfunction; P(Aa)O<sub>2</sub> can precisely evaluate pulmonary gas exchange capacity, which correlates well with pulmonary oxygen level and function <xref ref-type="bibr" rid="ridm1841430676">7</xref>,<xref ref-type="bibr" rid="ridm1841356420">21</xref>. Thus,              monitoring P(Aa)O<sub>2</sub> can help evaluate dynamic changes in pulmonary lesions in ARDS patients, which is                    advantageous in individual management of ARDS.</p>
      <p>As a common diagnostic and risk stratification indicator for ARDS, OI provides a reference for medical treatment <xref ref-type="bibr" rid="ridm1841355268">22</xref>. In the present study, P(Aa)O<sub>2</sub> correlated  negatively with OI (<italic>r </italic>= –0.555, <italic>P</italic> &lt;0.001), indicating that P(Aa)O<sub>2</sub> has diagnostic ability for ARDS. This investigation showed that when P(Aa)O<sub>2</sub> was greater than 214.70 mmHg, the sensitivity and specificity of P(Aa)O<sub>2</sub> were 89.50% and 85.00%, respectively, in diagnosing ARDS; this finding underlines the clinical value of P(Aa)O<sub>2</sub> in such diagnosis. P(Aa)O<sub>2</sub> is appropriate owing to the pathology of ARDS, which is an oxygen exchange disorder caused by inflammation: P(Aa)O<sub>2</sub> has high sensitivity in reflecting pulmonary oxygen exchange. Some studies have reported the significance of P(Aa)O<sub>2</sub> for ARDS. Wang and Associates suggested that P(Aa)O<sub>2</sub> can provide a clear early warning for ARDS in patients with severe pneumonia <xref ref-type="bibr" rid="ridm1841352892">23</xref>,<xref ref-type="bibr" rid="ridm1841350156">24</xref>. P(Aa)O<sub>2</sub> can be used for the stratified diagnosis and guiding        treatment of ARDS patients <xref ref-type="bibr" rid="ridm1841363116">25</xref>. Yang et al. suggested that P(Aa)O<sub>2</sub> may play an important role in indicating the                 severity of ARDS in patients with pulmonary infection; it can also be used to assess the risk of fatality <xref ref-type="bibr" rid="ridm1841360308">26</xref>. P(Aa)O<sub>2</sub> may be employed as an important reference indicator for judging clinical efficacy. Zhang et al. found that P(Aa)O<sub>2</sub> dynamic monitoring was effective in making a dynamic assessment for pulmonary disease and could be used to guide clinical treatment <xref ref-type="bibr" rid="ridm1841340892">27</xref>. Yu et al. <xref ref-type="bibr" rid="ridm1841370484">20</xref> and Shen et al. <xref ref-type="bibr" rid="ridm1841338660">28</xref> suggested that P(Aa)O<sub>2</sub> can guide the withdrawal of                mechanical ventilation in ARDS patients. The clinical               application of P(Aa)O<sub>2</sub> for ARDS patients was confirmed in the present study.</p>
      <p>Some limitations of this study deserve mention. We had relatively few cases, and we selected only sepsis patients from one central ICU; their conditions were quite severe, so there could have been some significant                 deviation in the cutoff value we determined. We measured P(Aa)O<sub>2</sub> directly by blood gas analysis with arterial blood, which was simple, convenient, and repeatable. However, whether P(Aa)O<sub>2</sub> is as convenient a measure as OI                  requires further prospective clinical studies regarding the ability to assess ARDS and its practicability.</p>
    </sec>
    <sec id="idm1842710524" sec-type="conclusions">
      <title>Conclusion</title>
      <p>P(Aa)O<sub>2</sub> is a good diagnostic index for pneumonia patients with ARDS complications.</p>
    </sec>
    <sec id="idm1842710452">
      <title>Declarations</title>
    </sec>
    <sec id="idm1842708148">
      <title>Competing Interests</title>
      <p>The authors have no conflicts of interest to                declare</p>
    </sec>
    <sec id="idm1842709876">
      <title>Funding</title>
      <p>Guizhou Science and Technology Support Plan（(2020) 4Y139）;Qiandongnan Miao and Dong                    Autonomous Prefecture Science and Technology Support Plan（(2021)12）; Cultivation of High-Level Innovative Talents in Guizhou Province</p>
    </sec>
    <sec id="idm1842708292">
      <title>Ethical Approval </title>
      <p>The research was approved by the medical ethics committee of the people's Hospital of Qiandongnan Miao and Dong Autonomous Prefecture. </p>
    </sec>
  </body>
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