Multivariable logistic regression analyses of NL % and lung physiology variables for single or composite unit stages in the Japanese and GAP staging systems.

<p>Multivariable logistic regression analyses of NL % and lung physiology variables for single or composite unit stages in the Japanese and GAP staging systems.</p

Multivariable logistic regression analyses of CT image indices for single or composite unit stages in the Japanese and GAP staging systems.

<p>Multivariable logistic regression analyses of CT image indices for single or composite unit stages in the Japanese and GAP staging systems.</p

Multivariable logistic regression analyses of NL and NL % for single or composite unit stages in the Japanese and GAP staging systems.

<p>Multivariable logistic regression analyses of NL and NL % for single or composite unit stages in the Japanese and GAP staging systems.</p

Volumetric analysis of normally attenuated lung.

<p>Chest computed tomography (CT) image of a 79-year-old man with IPF showing UIP pattern. This CT slice shows peripheral honeycomb lung predominantly on the right side (A). The CT image showing extracted whole lungs (in green) (B). The volume of the whole lungs (WL) is 2,438 milliliter (mL). The CT image showing normally attenuated lung, as defined between −950 Hounsfield units (HU) and −701 HU (in yellow) (C). The volume of normally attenuated lung (NL) is 1,346 mL. Although some parts of honeycombing are marked as normally attenuated lung (in yellow) by the workstation, most areas of normally attenuated lung are considered to be identical to normal lung tissue. The yellow area under the histogram curve represents the NL (D). The percentage of NL (NL%) is 55.2%. Forced vital capacity and diffusing capacity of the lungs for carbon monoxide of this patient are 1.59 L (52.1%, %predicted) and 6.6 mL/min/mmHg (59.2%, %predicted), respectively. His partial pressure of arterial oxygen is 65.9 Torr, and the lowest percutaneous oxygen saturation is 84% during the 6-min walk test. The patient was classified in Japanese stage IV and GAP stage II.</p

Clinical and physiologic data of the study population.

<p>Clinical and physiologic data of the study population.</p

The AUC values of CT imaging indices for clinical staging of IPF.

<p>The area under the curve (AUC) values of CT imaging indices, including mean CT value of the whole lungs (MCT), the volume of the whole lungs extracted from CT imaging (WL), the volume of normally attenuated lung (NL), and the percentage of the volume of normally attenuated lung in whole lungs from CT imaging (NL%), are shown.</p

Japanese staging system [11].

<p>Japanese staging system [<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0152505#pone.0152505.ref011" target="_blank">11</a>].</p

ROC curves of NL%.

<p>The receiver operating characteristic (ROC) curves of the percentage of the volume of normally attenuated lung in whole lungs from CT imaging (NL%) for clinical composite unit stages of Japanese stage II/III/IV (A), Japanese stage III/IV (B), and GAP stage II/III (C). The values of AUC are 0.864, 0.822, and 0.844, respectively.</p

Respiratory reflexes in humans, guinea pigs, wild-type (WT) mice, and <i>Ttll1</i>^{<i>−/−</i>} mice.

<p>(A−D): Charts exhibiting airflow patterns of respiratory reflexes. Expiratory flow is indicated by the plus sign (upward) and inspiratory flow is indicated by the minus sign (downward). Airflow patterns of human reflexes (A). Airflow through the nose and mouth induced by cough, sneeze, and the expiration reflex was recorded using a spirometer (n = 3). Cough and the expiration reflex were evoked by inhaled capsaicin. Sneeze was evoked by mechanical stimuli applied by rubbing the nasal cavity with a tapered tissue paper. Airflow patterns of reflexes in guinea pigs (B) and WT mice (C; see <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0141823#pone.0141823.s002" target="_blank">S1</a>–<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0141823#pone.0141823.s005" target="_blank">S4</a> Videos). Airflows of cough and sneeze were analyzed using a whole body plethysmograph (WBP). Cough was evoked by inhaled citric acid in guinea pigs and capsaicin in mice. Sneeze was induced by intranasal instillation of ovalbumin in sensitized animals. In (A–C), cough and sneeze showed one-peak and two-peak expiration patterns with preceding inspiration, respectively. Airflow patterns of reflexes in <i>Ttll1</i>^−/− mice (D; see <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0141823#pone.0141823.s006" target="_blank">S5</a>–<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0141823#pone.0141823.s008" target="_blank">S7</a> Videos). These reflexes were analyzed by WBP and classified into three patterns: (i) one-peak expiration with preceding inspiration, (ii) two-peak expiration with preceding inspiration, and (iii) one-peak expiration without preceding inspiration. Patterns (i) and (ii) corresponded to cough and sneeze patterns, respectively. #: expiration during eupneic breathing, which was not accompanied by characteristic sound and motion. (E) Representative photos recorded by videofluoroscopy. The <i>Ttll1</i>^−/− mice were placed in a WBP device. Inspiration and expiration phases in cough and normal breathing are shown. Solid lines indicate the diaphragm of the <i>Ttll1</i>^−/− mice (see <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0141823#pone.0141823.s009" target="_blank">S8 Video</a>). (F) The bar graph shows the calculated amplitude of the diaphragm while coughing [= b–a in (E)] and normal breathing [= d–c in (E)]. The maximal distance [two-headed arrow in (E)] between the dotted line connecting the costophrenic angles and the diaphragm [solid line in (E)] as measured during inspiration and expiration while coughing and normal breathing. Diaphragm motion in the <i>Ttll1</i>^−/− mice was larger during coughing than during normal breathing (n = 3; mean ± SEM; *P = 0.006 by two-tailed Student's t-test). (G) Number of respiratory reflexes of the <i>Ttll1</i>^−/− mice in ten minutes (mean ± SEM, n = 10).</p

Representative images of immunostaining of purified blood eosinophils and non-eosinophils from healthy controls.

<p>Case 1 (46-year-old female), case 2 (36-year-old female), case 3 (35-year-old male). Column A: staining with anti-FKBP51 antibody, column B: merged image of staining with anti-major basic protein antibody (MBP) and anti-FKBP51 antibody. Red indicates MBP, and green indicates FKBP51.</p