UNIVERSITÁ DEGLI STUDI DI MILANO DOTTORATO IN .UNIVERSITÁ DEGLI STUDI DI MILANO DOTTORATO IN SCIENZE

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UNIVERSIT DEGLI STUDI DI MILANO

DOTTORATO IN SCIENZE FISIOLOGICHE MORFORLOGICHE E

DELLO SPORT

Sezione di Fisiologia

CICLO XXVIII

Tesi di Dottorato di Ricerca

DIAPHRAGMATIC MOBILITY, LUNG HYPERINFLATION AND

EFFECTS OF THE PULMONARY REHABILITATION

Dottorando:

Camilo Corbellini

Matricola: R10266

Tutor: Dott. Luciano Zocchi

Coordinatore: Prof.Michele Mazzanti

Anno Accademico 2014-2015

UNIVERSIT DEGLI STUDI DI MILANO

DOTTORATO IN SCIENZE FISIOLOGICHE MORFORLOGICHE E

DELLO SPORT

Sezione di Fisiologia

CICLO XXVIII

Tesi di Dottorato di Ricerca

DIAPHRAGMATIC MOBILITY, LUNG HYPERINFLATION AND

EFFECTS OF THE PULMONARY REHABILITATION

Camilo Corbellini

Anno Accademico 2014-2015

ACKNOWLEDGEMENTS

I want to thanks all my patients for every single breath that I borrowed from

their lives.

To Elena and Giacomo, who gives me, everyday, love and strength to keep

breathing.

To my dear colleagues who helped me on the data collection

To my beloved mom and dad

All we need is love

love is all we need!

THE BEATLES

Hey holets go!!!

RAMONES

INDEX

I. ABREVIATION LIST ........................................................................................................................... I

II. FIGURE LIST .................................................................................................................................... III

III. TABLE LIST ....................................................................................................................................... IV

ABSTRACT .................................................................................................................................................. - 1 -

1. INTRODUCTION ............................................................................................................................. - 2 -

2. THE DIAPHRAGM .......................................................................................................................... - 4 -

Action of the diaphragm. ........................................................................................................................... - 5 -

Biology and functional properties ............................................................................................................. - 7 -

3. THE HUMAN BREATHING ........................................................................................................... - 8 -

The respiratory muscles. ............................................................................................................................ - 8 -

The chest wall. ........................................................................................................................................... - 8 -

4. CHRONIC OBSTRUCTIV PULMONARY DISEASE ................................................................ - 10 -

Definition ................................................................................................................................................. - 10 -

Lung Hyperinflation ................................................................................................................................ - 10 -

Assessment and severity .......................................................................................................................... - 13 -

5 THE DIAPHRAGM IN COPD. ...................................................................................................... - 14 -

The diaphragm in COPD: Biology and functional properties ................................................................. - 16 -

6. DIAPHRAGM ASSESMENT AND M MODE ULTRASONOGRAPHY .................................... - 20 -

7. PULMONARY REHABILITATION ............................................................................................ - 24 -

8. OBJECTIVES ................................................................................................................................. - 27 -

Main objective ......................................................................................................................................... - 27 -

Secondary objectives ............................................................................................................................... - 27 -

9. METHODS ...................................................................................................................................... - 28 -

Study design ............................................................................................................................................ - 28 -

Patients: ................................................................................................................................................... - 28 -

Exclusion criteria ..................................................................................................................................... - 28 -

Study methods and protocols: ................................................................................................................. - 28 -

Statistical analyses: .................................................................................................................................. - 31 -

Ethical aspects ......................................................................................................................................... - 32 -

10. RESULTS ........................................................................................................................................ - 33 -

11. DISCUSSION ................................................................................................................................. - 44 -

12. CONCLUSION .............................................................................................................................. - 48 -

13. REFERENCES ................................................................................................................................ - 49 -

I

I. ABREVIATION LIST

ABGA: arterial blood gases analyzes

BMI: body mass index

bpm: beats per minutes

CI: confidence interval

COPD: Chronic Obstructive Pulmonary Disease

CS: mitochondrial activity

DL,CO: carbon monoxyde lung difusion

DM: diaphragmatic mobility

EELV: end expiratory lung volume

ERV: expiratory residual volume

f: respiratory frequency

FEF 25-75 : forced expiratory flow on 25% to 75%

FEV1: forced expiratory volume on 1sec; cm

FRC: functional residual capacity

FVC: forced vital capacity; centimeters

GOLD. Global Initiative for Chronic Obstructive Lung Disease

HC: healthy controls

HCO3 : bicarbonate

HR: heart rate

IC: inspiratory capacity

ICC: intraclass correlation coefficient

IRV: inspiratory residual volume

Kg: kilograms

L: liters

LDH: lactate dehydrogenase

II

LOA: limits of agreement

m: meters

MBS: modified borg scale

MHC: myosin heavy chains

MLC: myosin light chain

mmHg: millimeter of mercury

mpm: movements per minute

PaCO2: Partial arterial pressure of carbon dioxide

pH: Hydrogenionic potential

PR: Pulmonary rehabilitation

RV: residual volume

s: seconds

SD: standard deviation

SDP: slow deep inspiration;

SEM: standard error of measurement

SpO2: partial oxygen saturation

TGV: total gas volume

TLC: total lung capacity

VC: vital capacity

Vt. Tidal volume

Yrs: years

III

II. FIGURE LIST

Figure 1: S chematic representation of the human diaphragm.

Figure 2: Schematic representation of the diaphragm apposition zone to the rib cage.

Figure 3: Histopathology of COPD small airways.

Figure 4: Schematic of mechanical effects of COPD exacerbation.

Figure 5: Volume tracing from a patient with severe COPD who demonstrated ventilatory

dependent dynamic hyperinflation.

Figure 6: Three-dimensional reconstruction of diaphragm in one control subject and one patient

COPD patient.

Figure 7 Distribution of the I, IIa, and IIx isoforms of the MHC in the costal diaphragm.

Figure 8: Proportion of MyHC-1 isoform in biopsy on muscles from healthy subjects and patients

with chronic obstructive pulmonary disease.

Figure 9: Correlation between Inspiratory capacity/ total lung capacity ratio and the diaphragmatic

mobility in COPD patients.

Figure 10: Correlation between the vital capacity and the diaphragmatic mobility.

Figure 11: A spectrum of support for chronic obstructive pulmonary disease.

Figure 12: Schematic illustration of the area displaced by diaphragm movement during both

inspiration and expiration.

Figure 13: Schematic demonstration of the US technique.

Figure 14: Schematic representation of the measurement technique on resting and forced

inspiratory breath.

Figure 15: Flow chart presenting the sample characteristics, its classification and outcomes.

Figure 16: Correlation between the dia