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Lung function and physiology

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  • 1. WHAT 2010
    • LUNG FUNCTION
    University of Verona, Italy Attilio Boner
  • 2. spirometri
  • 3. Spirometry Don’t blow it! Lange Chest 2009:136:608 Technique for performing forced exhalation maneuver. The subject starts with tidal breathing and, when ready, inhales maximally and rapidly. Forced exhalation begins with a “blast” and continues until plateau is seen on the volume-time curve or the patient is unable to continue.
  • 4. Spirometry Don’t blow it! Lange Chest 2009:136:608 Acceptable and unacceptable flow-volume loops normal cough in first second premature ending submaximal effort hesitation at start
  • 5. Spirometry Don’t blow it! Lange Chest 2009:136:608
  • 6. Spirometry Don’t blow it! Lange Chest 2009:136:608 Back-extrapolation. To determine a new time-zero, back-extrapolation is performed using the steepest part of the slope on the volume-time curve, the PEF. This will minimize inaccuracies in FEV 1 due to hesitation at the start of exhalation.
  • 7. Spirometry Don’t blow it! Lange Chest 2009:136:608 Back-extrapolation. To determine a new time-zero, back-extrapolation is performed using the steepest part of the slope on the volume-time curve, the PEF. This will minimize inaccuracies in FEV 1 due to hesitation at the start of exhalation. Extrapolated Volume ( EV ) must be < 5% of FVC or 0.15 L, whichever is greater
  • 8. Spirometry Don’t blow it! Lange Chest 2009:136:608
  • 9. Accuracy of Whole-Body Plethysmography Requires Biological Calibration Poorisrisak Chest 2009;135:1476
    • Background:
    • Specific airway resistance (sRaw) measured by whole-body plethysmography in young children is increasingly used in research and clinical practice. The method is precise and feasible. However, there is no available method for calibration of the resistance measure , which raises concern of accuracy. Our aim was to determine the agreement of sRaw measurements in six centers and expand normative sRaw values for nonasthmatic children including these centers.
  • 10.
    • 7 healthy young children were brought to each of the six centers for sRaw measurements
    • 105 healthy preschool children were recruited locally for sRaw measurements
    Center agreement study: least squares mean for sRaw for six centers with 95% confidence interval (CI) [software versions are indicated in parentheses]. Accuracy of Whole-Body Plethysmography Requires Biological Calibration Poorisrisak Chest 2009;135:1476
  • 11.
    • 7 healthy young children were brought to each of the six centers for sRaw measurements
    • 105 healthy preschool children were recruited locally for sRaw measurements
    Center agreement study: least squares mean for sRaw for six centers with 95% confidence interval (CI) [software versions are indicated in parentheses]. Accuracy of Whole-Body Plethysmography Requires Biological Calibration Poorisrisak Chest 2009;135:1476 The sRaw of the 7 children study group was significantly lower at 2 centers compared with the other four centers, and one center had significantly higher sRaw than all the other centers (p<0.05).
  • 12.
    • 7 healthy young children were brought to each of the six centers for sRaw measurements
    • 105 healthy preschool children were recruited locally for sRaw measurements
    Center agreement study: least squares mean for sRaw for six centers with 95% confidence interval (CI) [software versions are indicated in parentheses]. Accuracy of Whole-Body Plethysmography Requires Biological Calibration Poorisrisak Chest 2009;135:1476 Error in the factory settings of the software was subsequently discovered in one of the deviating centers.
  • 13. Normative study: healthy sRaw data against height for five centers. Normative data from the multicenter study (five centers) and the previous study by Klug and Bisgaard. Accuracy of Whole-Body Plethysmography Requires Biological Calibration Poorisrisak Chest 2009;135:1476
  • 14. Normative study: healthy sRaw data against height for five centers. Normative data from the multicenter study (five centers) and the previous study by Klug and Bisgaard. Accuracy of Whole-Body Plethysmography Requires Biological Calibration Poorisrisak Chest 2009;135:1476 Normative data (105 preschool children) were generated and were without significant difference between centers and independent of height, weight, age, and gender.
  • 15. valori normali
  • 16. Rationale : Advances in spirometry measurement techniques have made it possible to obtain measurements in children as young as 3 years of age; however, in practice, application remains limited by the lack of appropriate reference data for young children, which are often based on limited population-specific samples. Objectives : We aimed to build on previous models by collating existing reference data in young children (aged 3–7 yr), to produce updated prediction equations that span the preschool years and that are also linked to established reference equations for older children and adults. Spirometry Centile Charts for Young Caucasian Children Stanojevic AJRCCM 2009:180:547
  • 17.
    • Children aged 3–7 years (n = 3,777) from 15 centers across 11 countries.
    Predicted values for ( a ) FEV 0.75 /FVC and ( b ) FEV 1 /FVC, adjusted for the median age at each height. Both ratios are greater for females at all ages. Height (cm) Spirometry Centile Charts for Young Caucasian Children Stanojevic AJRCCM 2009:180:547
  • 18. Risk associated with poor lung function
  • 19. Background: Little is known about the perception of airflow obstruction in patients hospitalized for acute asthma. Objectives: To evaluate patient perception of airflow obstruction at hospital discharge and at a 2-week follow-up visit and to determine whether symptom control and/or severity of airflow obstruction identified patients at risk for acute asthma after discharge. Perception of airflow obstruction in patients hospitalized for acute asthma Davis Ann Allergy Asthma Immunol 2009;102:455
  • 20.
    • FEV 1 % predicted at discharge and 2 weeks after discharge.
    • Perception of airflow obstruction (symptom control vs FEV 1 % predicted) and perception of change in airflow obstruction (change in symptom control vs % change in FEV 1 ) between the 2 visits.
    • 51 participants.
    Change in symptom control was not significantly associated with change in airflow obstruction ( P =0.20), indicating poor perception of change in airflow obstruction. Perception of airflow obstruction in patients hospitalized for acute asthma Davis Ann Allergy Asthma Immunol 2009;102:455
  • 21.
    • FEV 1 % predicted at discharge and 2 weeks after discharge.
    • Perception of airflow obstruction (symptom control vs FEV 1 % predicted) and perception of change in airflow obstruction (change in symptom control vs % change in FEV 1 ) between the 2 visits.
    • 51 participants.
    Greater airflow obstruction at follow-up ( P =0.02) and a smaller improvement in airflow obstruction ( P =0.03), but not symptom control, were associated with a higher risk of acute asthma after discharge Perception of airflow obstruction in patients hospitalized for acute asthma Davis Ann Allergy Asthma Immunol 2009;102:455
  • 22. Perception of airflow obstruction in patients hospitalized for acute asthma Davis Ann Allergy Asthma Immunol 2009;102:455 AT DISCHARGE AT DISCHARGE AT FOLLOW-UP AT FOLLOW-UP (A) Mean Asthma Control Questionnaire symptom score and (B) mean FEV 1 % pred in participants with and without subsequent acute asthma.
  • 23. Perception of airflow obstruction in patients hospitalized for acute asthma Davis Ann Allergy Asthma Immunol 2009;102:455 AT DISCHARGE AT DISCHARGE AT FOLLOW-UP AT FOLLOW-UP Only a spirometry performed 2 weeks after discharge identified subjects at risk of subsequent asthma. (A) Mean Asthma Control Questionnaire symptom score and (B) mean FEV 1 % pred in participants with and without subsequent acute asthma.
  • 24.
    • Approximately 1 in 5 participants had an episode of acute asthma within 90 days of hospital discharge.
    • Interestingly, neither the level of asthma symptom control (evaluated with ACT) nor the severity of airflow obstruction at discharge identified participants at higher risk for an acute asthma event.
    • In contrast, more severe airflow obstruction at the 2-week follow-up visit or a smaller improvement in airflow obstruction between the visits (but not asthma symptom control) was significantly associated with an increased risk of acute asthma.
    Perception of airflow obstruction in patients hospitalized for acute asthma Davis Ann Allergy Asthma Immunol 2009;102:455
  • 25.
    • Approximately 1 in 5 participants had an episode of acute asthma within 90 days of hospital discharge.
    • Interestingly, neither the level of asthma symptom control (evaluated with ACT) nor the severity of airflow obstruction at discharge identified participants at higher risk for an acute asthma event.
    • In contrast, more severe airflow obstruction at the 2-week follow-up visit or a smaller improvement in airflow obstruction between the visits (but not asthma symptom control) was significantly associated with an increased risk of acute asthma.
    An asthmatic patients admited to hospital should have a spirometry two weeks after discharge! Perception of airflow obstruction in patients hospitalized for acute asthma Davis Ann Allergy Asthma Immunol 2009;102:455
  • 26. Lung function predicts lung cancer risk in smokers: a tool for targeting screening programmes Calabrò ERJ 2010:35:146
    • 3,806 heavy smokers undergoing annual chest computed tomography screening.
    • 57 lung cancer cases and 3,749 subjects without cancer.
    OR for LUNG CANCER 2.45 2.90 <90% <70% 3.0 – 2.5 – 2.0 – 1.5 – 1.0 – 0.5 – 0 IN SUBJECTS WITH FEV 1 % PREDICTED
  • 27. Lung function predicts lung cancer risk in smokers: a tool for targeting screening programmes Calabrò ERJ 2010:35:146
    • 3,806 heavy smokers undergoing annual chest computed tomography screening.
    • 57 lung cancer cases and 3,749 subjects without cancer.
    OR for LUNG CANCER 2.45 2.90 <90% <70% 3.0 – 2.5 – 2.0 – 1.5 – 1.0 – 0.5 – 0 Even a relatively small reduction in FEV 1 % pred is a significant predictor of increased lung cancer risk. IN SUBJECTS WITH FEV 1 % PREDICTED
  • 28. Piccole vie aree
  • 29. lung function non-collaborante
  • 30. The potential use of spirometry during methacholine challenge test in young children with respiratory Vilozni, Ped Pul 2009;44:720 Background :The concentration of methacholine that causes a fall of 20% from baseline forced expiratory volume in the first second (PC20-FEV 1 ) in the methacholine challenge test (MCT) is not usually considered a diagnostic tool in preschool children since PC20-FEV 1 may not be achievable <6 years of age.
  • 31.
    • 3- to 6-year-old children
    • inhaled triple-concentration increments [0.057-13.925 mg] of methacholine solution.
    • 84 children previously diagnosed with asthma (asthmatics) and 48 with prolonged cough (coughers).
    10 – 9 – 8 – 7 – 6 – 5 – 4 – 3 – 2 – 1 – 0 1.48 9.45 Asthmatics Coughers PC25 FEV 0.5 p <0.0001 The potential use of spirometry during methacholine challenge test in young children with respiratory Vilozni, Ped Pul 2009;44:720
  • 32.
    • 3- to 6-year-old children
    • inhaled triple-concentration increments [0.057-13.925 mg] of methacholine solution.
    • 84 children previously diagnosed with asthma (asthmatics) and 48 with prolonged cough (coughers).
    10 – 9 – 8 – 7 – 6 – 5 – 4 – 3 – 2 – 1 – 0 1.48 9.45 Asthmatics Coughers PC25 FEV 0.5 p <0.0001 The potential use of spirometry during methacholine challenge test in young children with respiratory Vilozni, Ped Pul 2009;44:720 A cut-off at 2.2 mg/ml for PC25-FEV 0.5 had 73.8% sensitivity and 72.9% specificity, for clinical diagnosis of asthma.
  • 33. Risposta ai broncodilatatori
  • 34. An elevated bronchodilator response predicts large airway inflammation in mild asthma Puckett , Ped Pul 2010;45:174
    • Bronchodilator response (BDR).
    • eNO signal can be partitioned into its proximal [J'aw NO (nl/sec)] and distal contributions [CA NO (ppb)].
    • 179 children with mild asthma (69 steroid naïve).
    ICS naive ICS treated
  • 35. An elevated bronchodilator response predicts large airway inflammation in mild asthma Puckett , Ped Pul 2010;45:174
    • Bronchodilator response (BDR).
    • eNO signal can be partitioned into its proximal [J'aw NO (nl/sec)] and distal contributions [CA NO (ppb)].
    • 179 children with mild asthma (69 steroid naïve).
    ICS naive ICS treated
  • 36. An elevated bronchodilator response predicts large airway inflammation in mild asthma Puckett , Ped Pul 2010;45:174
    • Bronchodilator response (BDR).
    • eNO signal can be partitioned into its proximal [J'aw NO (nl/sec)] and distal contributions [CA NO (ppb)].
    • 179 children with mild asthma (69 steroid naïve).
    ICS naive ICS treated BDR reflects inflammation in the large airways, and may be an effective clinical tool to predict elevated large airway inflammation.
  • 37. Riduzione di funzionalità nel tempo
  • 38. Association of FVC and Total Mortality in US Adults With Metabolic Syndrome and Diabetes Mu Lee Chest 2009;136:171
    • 5,633 US adults (age range, 18 to 79 years) never-smokers and without cardiovascular or obstructive lung disease.
    • FVC categories: - low, ≤85% pred; - intermediate, 86 to 94%; - high, ≥95% pred.
    • Metabolic syndrome (MetS) and diabetes mellitus (DM).
    • The prevalence of DM and MetS significantly increased as predicted FVC decreased (p < 0.01).
    • Mortality rates increased in a stepwise manner as predicted FVC decreased in those patients with neither MetS nor DM, MetS, and DM.
  • 39. Association of FVC and Total Mortality in US Adults With Metabolic Syndrome and Diabetes Mu Lee Chest 2009;136:171
  • 40. Association of FVC and Total Mortality in US Adults With Metabolic Syndrome and Diabetes Mu Lee Chest 2009;136:171 In persons with MetS, a reduced FVC is associated with further increases in mortality, suggesting that the evaluation of lung function may be useful for risk stratification in those with MetS.
  • 41. A New Breath-Holding Test May Noninvasively Reveal Early Lung Abnormalities Caused by Smoking and/or Obesity Inoue Chest 2009;136:545
    • 38 healthy subjects
    • 46 smokers
    • 18 overweight nonsmokers ( BMI≥25 kg/m 2 )
    • 19 overweight smokers
    • 8 ex-smokers
    • A modified pulse oximeter was employed for measuring the fall in pulse oximetric saturation caused by 20-s breath-holding (dSpO 2 ) at resting end expiration in the sitting posture
    A new test that measures oxygen saturation during breath-holding reveals early lung abnormalities in subjects who either smoke or are overweight, especially if these factors are combined.
  • 42. Polygraph tracings of four sample subjects in the four group A New Breath-Holding Test May Noninvasively Reveal Early Lung Abnormalities Caused by Smoking and/or Obesity Inoue Chest 2009;136:545
  • 43. physiology
  • 44. Higher pulmonary dead space may predict prolonged mechanical ventilation after cardiac surgery Thida Ong Ped Pul 2009;44:457
    • The non-invasive cardiac output (NICO) monitor (Respironics Novametrix, Inc., Wallingford, CT) was used to measure pulmonary dead space fraction.
    • The NICO monitor measures carbon dioxide (CO 2 ) elimination and integrates an average of breath to breath measurements over 1 min to calculate mixed expired CO 2 (PeCO 2 ).
    • Using the Enghoff modification of the Bohr equation, PeCO 2 and a simultaneous arterial blood gas measurement are used to calculate the physiologic pulmonary dead space fraction:
    • Pulmonary dead space fraction =
    PaCO2 - PeCO2 PaCO2      TO P      ABSTRACT     ME THODS     RE SULTS     DI SCUSSION     Su pport statement     St atement of interest     AC KNOWLEDGEMENTS     RE FERENCES      TO P      ABSTRACT     ME THODS     RE SULTS     DI SCUSSION     Su pport statement     St atement of interest     AC KNOWLEDGEMENTS     RE FERENCES
  • 45. Higher pulmonary dead space may predict prolonged mechanical ventilation after cardiac surgery Thida Ong Ped Pul 2009;44:457
    • The non-invasive cardiac output (NICO) monitor (Respironics Novametrix, Inc., Wallingford, CT) was used to measure pulmonary dead space fraction.
    • The NICO monitor measures carbon dioxide (CO 2 ) elimination and integrates an average of breath to breath measurements over 1 min to calculate mixed expired CO 2 (PeCO 2 ).
    • Using the Enghoff modification of the Bohr equation, PeCO 2 and a simultaneous arterial blood gas measurement are used to calculate the physiologic pulmonary dead space fraction:
    • Pulmonary dead space fraction =
    PaCO2 - PeCO2 PaCO2 Physiologically, pulmonary dead space is the portion of ventilation that is unable to participate in gas exchange and is essentially wasted.      TO P      ABSTRACT     ME THODS     RE SULTS     DI SCUSSION     Su pport statement     St atement of interest     AC KNOWLEDGEMENTS     RE FERENCES      TO P      ABSTRACT     ME THODS     RE SULTS     DI SCUSSION     Su pport statement     St atement of interest     AC KNOWLEDGEMENTS     RE FERENCES
  • 46.
    • Pulmonary dead space fraction in 52 intubated, pediatric patients within 24 hr postoperative from congenital heart surgery.
    Pulmonary dead space fraction is elevated in patients requiring mechanical ventilation for 48 hr or longer. p=0.0004 Higher pulmonary dead space may predict prolonged mechanical ventilation after cardiac surgery Thida Ong Ped Pul 2009;44:457      TO P      ABSTRACT     ME THODS     RE SULTS     DI SCUSSION     Su pport statement     St atement of interest     AC KNOWLEDGEMENTS     RE FERENCES      TO P      ABSTRACT     ME THODS     RE SULTS     DI SCUSSION     Su pport statement     St atement of interest     AC KNOWLEDGEMENTS     RE FERENCES
  • 47.
    • Pulmonary dead space fraction in 52 intubated, pediatric patients within 24 hr postoperative from congenital heart surgery.
    P=0.006 for trend Median duration of mechanical ventilation by tertile of dead space fraction. Higher pulmonary dead space may predict prolonged mechanical ventilation after cardiac surgery Thida Ong Ped Pul 2009;44:457      TO P      ABSTRACT     ME THODS     RE SULTS     DI SCUSSION     Su pport statement     St atement of interest     AC KNOWLEDGEMENTS     RE FERENCES      TO P      ABSTRACT     ME THODS     RE SULTS     DI SCUSSION     Su pport statement     St atement of interest     AC KNOWLEDGEMENTS     RE FERENCES
  • 48.
    • Pulmonary dead space fraction in 52 intubated, pediatric patients within 24 hr postoperative from congenital heart surgery.
    P=0.006 for trend Median duration of mechanical ventilation by tertile of dead space fraction. Higher pulmonary dead space may predict prolonged mechanical ventilation after cardiac surgery Thida Ong Ped Pul 2009;44:457 Pulmonary dead space fraction is a simple, easy-to-obtain measurement involving a sensor attached in-line to the mechanical ventilator that measures flow, pressure, and CO 2 elimination.      TO P      ABSTRACT     ME THODS     RE SULTS     DI SCUSSION     Su pport statement     St atement of interest     AC KNOWLEDGEMENTS     RE FERENCES      TO P      ABSTRACT     ME THODS     RE SULTS     DI SCUSSION     Su pport statement     St atement of interest     AC KNOWLEDGEMENTS     RE FERENCES
  • 49. Mechanisms that may contribute to elevated pulmonary dead space fraction in congenital heart disease:
    • Microvascular thrombosis during cardiac surgery due to
    • inflammation associated with cardiopulmonary bypass from surface and blood component interactions, non-pulsatile blood flow, regional perfusion disturbances, and ischemia-reperfusion insults.
    • 2. Poor pulmonary perfusion from low cardiac output or
    • hypotension.
    • 3. Residual shunt physiology as the shunt lesion may prevent some blood from reaching the lung to eliminate CO 2 .
    Higher pulmonary dead space may predict prolonged mechanical ventilation after cardiac surgery Thida Ong Ped Pul 2009;44:457      TO P      ABSTRACT     ME THODS     RE SULTS     DI SCUSSION     Su pport statement     St atement of interest     AC KNOWLEDGEMENTS     RE FERENCES      TO P      ABSTRACT     ME THODS     RE SULTS     DI SCUSSION     Su pport statement     St atement of interest     AC KNOWLEDGEMENTS     RE FERENCES
  • 50. Does the 6-min walk test correlate with the exercise stress test in children? Lesser , Ped Pul 2010;45:135
    • The 6-min walk test is easy to perform.
    • American Thoracic Society. ATS statement: guidelines for the six-minute walk test. Am J Respir Crit Care Med 2002;166:111–117.
    • The 6-min walk test does not measure maximal oxygen uptake or determine the mechanisms of exercise limitation.
    • Although the primary outcome routinely used in the 6-min walk test is the distance walked (6MWD), this measure does not take body weight into account and does not give an estimate of the energy output used during the test.
    • Cavagna and Margaria determined that the horizontal work of walking can be estimated as the product of distance traveled and body weight (6MWORK).
  • 51. Exercise Testing All subjects performed treadmill graded exercise stress testing. Subjects were asked to walk or run on a treadmill with initial speed of 1.9 kphr. The treadmill speed was increased gradually over the first 7 min of the test to a maximum of 7 kphr and then the grade on the treadmil was increased by 2.5% each minute to a maximum of 20%. Subjects were encouraged to exercise until exhaustion. Subjects breathed through a mouthpiece from which inspired and expired gas concentrations were continuously analyzed and tidal volumes were measured using a computerized breath-by-breath exercise system (Medgraphics, CardioO2, St. Paul, MN). Minute ventilation (V0E), oxygen consumption (V0O2), carbon dioxide excretion (V0CO2 ), RER (V0CO2=V0O2), and ventilatory equivalents for oxygen (V0E=V0O2 ) and carbon dioxide (V0E=V0CO2 ) were calculated on a breath-by-breath basis. Does the 6-min walk test correlate with the exercise stress test in children? Lesser , Ped Pul 2010;45:135
  • 52. Exercise Testing Heart rate was continuously monitored by electrocardiogram and oxygen saturation was determined by pulse oximeter (Capnocheck plus with oximetry, BCI international, Smiths Medical, Kent, UK). Effort was considered to be maximal if the highest observed heart rate was >170 bpm and the peak RER was 1.0. The V0O2 max was recorded as the highest achieved V0O2 during exercise, and the HR at V0O2 max and O2 pulse (V0O2 max/HR at V0O2 max) were also recorded. Anaerobic threshold (AT) was determined at the point at which V0CO2 increased non linearlycompared to V0O2, calculated by the exercisesystem (Medgraphics, CardioO2) and checked manually. Does the 6-min walk test correlate with the exercise stress test in children? Lesser , Ped Pul 2010;45:135
  • 53. Six-Minute Walk Test The 6-min walk test was conducted as per American Thoracic Society standards.1 Subjects were informed that the object of the test was to walk as far as possible for 6 min, and that they were permitted to slow down or rest when necessary. They were then asked to walk back and forth in the hallway for 6 min and standardized instructions were given before, during, and at the completion of the test.1 The investigator remained at one end of the hallway and did not walk with the subjects. The distance walked was recorded in meters (6MWD). To calculate the work of walking (6MWORK), 6MWD was converted to kilometers and multiplied by the weight in kilograms. Does the 6-min walk test correlate with the exercise stress test in children? Lesser , Ped Pul 2010;45:135
  • 54.  
  • 55.