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Cough reflex sensitivity and urge-to-cough deterioration in dementia with Lewy bodies

Takae Ebihara, Peijun Gui, Chika Ooyama, Koichi Kozaki, Satoru Ebihara
ERJ Open Research 2020 6: 00108-2019; DOI: 10.1183/23120541.00108-2019
Takae Ebihara
1Dept of Geriatric Medicine, Kyorin University School of Medicine, Tokyo, Japan
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  • For correspondence: takae-ebi@ks.kyorin-u.ac.jp
Peijun Gui
2Dept of Internal Medicine and Rehabilitation Science, Tohoku University Graduate School of Medicine, Sendai, Japan
3Dept of Rehabilitation Medicine, Beijing Friendship Hospital, Capital Medical University, Beijing, China
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Chika Ooyama
2Dept of Internal Medicine and Rehabilitation Science, Tohoku University Graduate School of Medicine, Sendai, Japan
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Koichi Kozaki
1Dept of Geriatric Medicine, Kyorin University School of Medicine, Tokyo, Japan
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Satoru Ebihara
2Dept of Internal Medicine and Rehabilitation Science, Tohoku University Graduate School of Medicine, Sendai, Japan
4Dept of Rehabilitation Medicine, Toho University Graduate School of Medicine, Tokyo, Japan
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  • FIGURE 1
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    FIGURE 1

    Flow diagram describing the study protocol. MMSE: mini mental state examination; RTI: respiratory tract infection; DLB: dementia with Lewy bodies; AD: Alzheimer's disease; UTC: urge-to-cough.

  • FIGURE 2
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    FIGURE 2

    Relationship between cognitive function and the cough reflex sensitivity, showing significant differences between a) the relationship between mini mental state examination (MMSE) score and log C2 (where C2=lowest concentration of inhaled citric acid that could induce ≥2 coughs) and b) the relationship between MMSE and log C5 (where C5=lowest concentration of inhaled citric acid that could induce ≥5 coughs).

  • FIGURE 3
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    FIGURE 3

    Comparison of cough reflex sensitivity among the control group, the Alzheimer's disease (AD) group and the dementia with Lewy bodies (DLB) group, showing: (a) the relationship of log C2 (where C2=lowest concentration of inhaled citric acid that could induce ≥2 coughs) for each group; (b) the relationship of log C5 (where C5=lowest concentration of inhaled citric acid that could induce ≥5 coughs) with each group. Two-way ANOVA showed significant differences in log C2 and log C5 between the DLB group and the control group or the AD group (p1=0.002 (a) and p1=0.0004 (b), as adjusted for gender). Post hoc tests showed significant differences in log C2 and log C5 between the DLB group and the control group or the AD group (p=0.003 and p=0.045, respectively (a) and p=0.001 and p=0.016, respectively (b), as adjusted for gender)

  • FIGURE 4
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    FIGURE 4

    Relationship between cognitive function and the urge-to-cough (UTC), showing: a) the relationship between mini mental state examination (MMSE) score and log Cu (where Cu=concentration of citric acid at a threshold of UTC), which illustrates significant differences; b) a comparison of log Cu between the control group, the Alzheimer's disease (AD) group and the dementia with Lewy bodies (DLB) group. Log Cu in the DLB group was significantly higher than in the control group and the AD group (p1=0.004, as adjusted for gender). Post hoc tests showed significant differences in log Cu between the DLB group and the control group or the AD group (p=0.008 and p=0.061, respectively).

  • FIGURE 5
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    FIGURE 5

    Relationship between (a) mini mental state examination (MMSE) score and the urge-to-cough (UTC) log–log scale slope of log Cu (where Cu=concentration of citric acid at a threshold of UTC), which illustrates significant differences; (b) comparison of the UTC log–log scale slope of log Cu among the control group, the Alzheimer's disease (AD) group and the dementia with Lewy bodies (DLB) group. There was no significant difference amongst the three groups (p=0.111).

Tables

  • Figures
  • TABLE 1

    Characteristics of patients stratified by sex

    CharacteristicMaleFemalep-value
    Participants n3239
    Dementia type n
     Control148
     AD921
     DLB910
    Age years76.47±8.2780.24±5.620.02
    BMI kg·m−222.10±3.2021.31±3.240.34
    Brinkman Index413.40±430.7813.57±44.28<0.01
    MMSE score23.19±6.1920.81±5.450.06
    FEV1 % predicted105.71±27.30114.57±30.950.19
    FVC % predicted91.36±18.9391.66±24.460.68
    FEV1/FVC %75.56±10.8080.21±13.240.04
    FEV1/FVC % predicted118.91±15.86112.50±18.580.1
    pH7.41±0.037.41±0.020.92
    PaO2 mmHg86.94±13.7487.72±7.950.39
    PaCO2 mmHg39.10±3.9039.86±3.400.58
    HCO3− mmol·L−124.48±2.7624.97±2.200.34

    Data are presented as mean±sd unless otherwise stated and were analysed using the Mann–Whitney test. p-Values in bold express significant difference (p<0.05). AD: Alzheimer's disease; DLB: dementia with Lewy bodies; BMI: body mass index; MMSE: mini mental state examination; FEV1: forced expiratory volume in 1 s; FVC: forced vital capacity; PaO2: arterial oxygen tension; PaCO2: arterial carbon dioxide tension.

    • TABLE 2

      Comparison of cough between male and female subjects

      CharacteristicMaleFemalep-value
      Patients n3239
      Dementia type n
       Control148
       AD921
       DLB910
      C2 log g·L−10.97±0.470.90±0.520.27
      C5 log g·L−11.16±0.511.10±0.490.5
      Cu log g·L−10.40±0.430.42±0.490.9
      UTC slope1.00±0.661.03±0.720.99

      Data are presented as mean±sd unless otherwise stated and were analysed using the Mann–Whitney test. p-Values less than 0.05 were deemed to represent significant difference. AD: Alzheimer's disease; DLB: dementia with Lewy bodies; Cx: lowest concentration of inhaled citric acid that could induce ≥x coughs; Cu: concentration of citric acid at a threshold of UTC; UTC: urge-to-cough.

      • TABLE 3

        Patients characteristics in the three study groups

        CharacteristicControlADDLBp-valuep1-value
        Patients n223019
        Sex (M/F) n/n14/89/219/10
        Age years76.64±6.3780.40±6.4377.67±8.700.1460.257
        BMI kg·m−222.08±3.5321.62±2.9221.26±3.450.7320.852
        Brinkman Index340.12±462.08110.19±221.91146.63±323.860.0630.349
        MMSE score27.82±2.2419.69±4.5019.25±6.25<0.001<0.001
        FEV1 % predicted109.66±19.91119.33±33.0395.48±29.620.0390.117
        FVC % predicted91.65±22.2598.18±19.9379.33±20.660.0250.064
        FEV1/FVC %80.91±10.6675.86±12.1077.72±14.650.3630.095
        FEV1/FVC % predicted121.37±12.89110.70±17.15115.56±22.070.1040.151
        pH7.41±0.027.41±0.027.42±0.030.1930.076
        PaO2 mmHg89.06±10.1285.81±11.5988.30±10.460.5670.514
        PaCO2 mmHg39.57±4.1839.29±3.9039.89±2.020.8790.683
        HCO3− mmol·L−124.44±1.6224.56±2.8725.58±2.390.3890.353

        Data are presented as mean±sd unless otherwise stated and were analysed using one-way ANOVA (p-values) or using two-way ANOVA when adjusting for gender (p1-values). Values are in bold show where significant differences were expressed (p<0.05 or p1<0.05). AD: Alzheimer's disease; DLB: dementia with Lewy bodies; BMI: body mass index; MMSE: mini mental state examination; FEV1: forced expiratory volume in 1 s; FVC: forced vital capacity; PaO2: arterial oxygen tension; PaCO2: arterial carbon dioxide tension.

        • TABLE 4

          Comparison of cough among the three study groups

          CharacteristicControlADDLBp-valuep1-value
          Patients n223019
          Sex (M/F) n/n14/89/219/10
          C2 log g·L−10.73±0.440.89±0.441.22±0.520.0030.002
          C5 log g·L−10.89±0.491.07±0.391.46±0.490.0010.0004
          Cu log g·L−10.24±0.450.36±0.370.67±0.520.0080.004
          UTC slope1.23±0.701.02±0.780.75±0.400.0830.116

          Data are presented as mean±sd and were analysed using one-way ANOVA (p-values) or using two-way ANOVA when adjusting for gender (p1-values). Values in bold show where significant differences were expressed (p<0.05 or p1<0.05). AD: Alzheimer's disease; DLB: dementia with Lewy bodies; Cx: lowest concentration of inhaled citric acid that could induce ≥x coughs; Cu: concentration of citric acid at a threshold of UTC; UTC: urge-to-cough.

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          Cough reflex sensitivity and urge-to-cough deterioration in dementia with Lewy bodies
          Takae Ebihara, Peijun Gui, Chika Ooyama, Koichi Kozaki, Satoru Ebihara
          ERJ Open Research Jan 2020, 6 (1) 00108-2019; DOI: 10.1183/23120541.00108-2019

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          Cough reflex sensitivity and urge-to-cough deterioration in dementia with Lewy bodies
          Takae Ebihara, Peijun Gui, Chika Ooyama, Koichi Kozaki, Satoru Ebihara
          ERJ Open Research Jan 2020, 6 (1) 00108-2019; DOI: 10.1183/23120541.00108-2019
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