Influencia del genero en las enfermedades respiratorias tributarias de rehabilitacion (cat)

Influència del gènere en
les malalties respiratòries
tributàries de rehabilitació
J. Roig, MD, PhD, FCCP
Servei de Pneumologia
Clínica Creu Blanca
Barcelona

Sexe i gènere en malaltia respiratòria
• MPOC
• Malaltia intersticial / fibrosi pulmonar
• Càncer de pulmó
• SAHS
• Sensibilitat química múltiple
• Exercici / Mind & Body

Boezen HM. Clin Chest Med 2004
Sex and gender differences
in lung development and
their
clinical significance

Boezen HM. Clin Chest Med 200
Stages of
prenatal,
perinatal,
and
postnatal
lung
developme
nt

Prenatal Household Air Pollution Is Associated with Impaired Infant
Lung Function with Sex-Specific Effects
Evidence from GRAPHS, a Cluster Randomized Cookstove Intervention Trial
• Sex-stratified analyses suggested that girls were
particularly vulnerable (time to peak tidal expiratory
flow to expiratory time: b =20.003, P = 0.05; respiratory
rate: b = 0.36, p= 0.01; minute ventilation: b = 11.25, p
= 0.01; passive respiratory compliance normalized for
body weight: b = 0.005, P = 0.01)
• Altered infant lung function may increase risk for
pneumonia in the first year of life
• Prenatal Household Air Pollution exposure is associated
with impaired infant lung function, especially in girls
Lee AG. AJRCCM 2019

Cleaning at Home and at Work in Relation to
Lung Function Decline and Airway Obstruction
Svanes O. Am J Respir Crit Care Med 2018
ECRHS = European Community Respiratory Health Survey.
As compared with women not engaged in cleaning (–FEV1=18.5ml/yr), FEV1 declined
more rapidly in women responsible for cleaning at home (22.1; p=0.01) and
occupational cleaners (22.4; p=0.03).
Associations of Decline in FEV1 and FVC with Cleaning at Home and
Occupational Cleaning in Women

Theoretical model of how exposures affect pulmonary
function throughout the life span
Eisner MD Am J Respir Crit Care Med 2010

Chronic Obstructive Pulmonary Disease
(COPD)
© 2017 Global Initiative for Chronic Obstructive Lung Disease
►COPD is currently the fourth leading cause of death in the world
►COPD is projected to be the 3rd leading cause of death by 2020
►> 3 million people died of COPD in 2012 accounting for 6% of all
deaths globally
►Globally, the COPD burden is projected to increase in coming
decades because of continued exposure to COPD risk factors and
aging of the population
Lozano R, Naghavi M, Foreman K, et al. Global and regional mortality from 235 causes of death for 20 age groups in 1990 and 2010: a systematic analysis
for the Global Burden of Disease Study 2010. Lancet 2012; 380(9859): 2095-128.
Mathers CD, Loncar D. Projections of global mortality and burden of disease from 2002 to 2030. PLoS Med 2006; 3(11): e44

Enf. cardiaca isquémica
Enf. cerebrovascular
Infección respiratoria
Enf. diarreicas
Trast. perinatales
EPOC
Tuberculosis
Sarampión
Accidentes de tráfico
Cáncer de pulmón
3ª
Cáncer gástrico
SIDA
Suicidio
1990 2020
Global Burden Disease
Mortalidad Global Prevista

Gender Differences in Symptoms and Care Delivery
for Chronic Obstructive Pulmonary Disease
Martinez CH. J Women Health 2012.

Rehabilitation, Education & Self-Management

COPD and Comorbidities
Some common comorbidities occurring in patients with COPD with stable
disease include:
► Cardiovascular disease (CVD)
► Heart failure
► Ischaemic heart disease (IHD)
► Arrhythmias
► Peripheral vascular disease
► Hypertension
► Osteoporosis
► Anxiety and depression
► COPD and lung cancer
► Metabolic syndrome and diabetes
► Gastroesophageal reflux (GERD)
► Bronchiectasis
► Obstructive sleep apnea

14
COPD and gender differences: an update
Aryal S. Translational Research 2013

Zein JG. Clin Chest Med 2019
Asthma over the Adult Life Course
Gender and Hormonal Influences
Population-based study using data collected from the Centers for Disease Control

Figure 2
CHEST 2017 151, 686-696DOI: (10.1016/j.chest.2016.10.031)
Age-adjusted relative risk of hospitalization for COPD according to pack-years
among smokers who inhaled, in the Copenhagen City Heart Study (n = 9,083).
Jenkins CR. BRN Rev 2018.

Figure 3
CHEST 2017 151, 686-696DOI: (10.1016/j.chest.2016.10.031)
Women and COPD

Figure 1
Women and COPD
Medical Research Council (MRC) Dyspnoea scores by sex. In each stage
females had worse scores than males (p < 0.0001)

Figure 1
Jenkins CR. Chest 2017
Improving the Management of COPD in Women
Mean St George’s Respiratory Questionnaire (SGRQ) scores according to sex (*P
< .05) in a study that included 90 patients with COPD (60 male subjects and 30
female subjects; mean age: 64 +/- 9 years) with a wide range of airway
obstruction disorders (mean FEV1: 56% +/- 19% of predicted).

Figure 1
Jenkins CR. Chest 2017
Aryal S. Transl Res 2013
Improving the Management of COPD in Women

MPOC i Asma
Gestació i infantesa
Nyklíček I. Mindfulness skills during pregnancy:
Prospective associations with mother's mood
and neonatal birth weight. J Psychosom Res
2018
Savran O. Early life insults as determinants of
chronic obstructive pulmonary disease in adult
life. Int J COPD 2018
Douros K. Prenatal Maternal Stress and the Risk
of Asthma in Children. Front Pediatr 2017

Estrés materno aumenta problemas respiratorios
Una iniciativa de la Fundación Bancaria ”la Caixa” y el grupo de investigación de
BCNatal (Hospital Clínic – Hospital Sant Joan de Déu – Univ de Barcelona) con el
equipo de Instituto Esmindfulness - Estudio IMPACT BCN.
Douros y cols , 2017 - Front. Pediatr., Prenatal Maternal Stress and the Risk of Asthma in Children

Age-associated changes in the impact of sex steroids on
influenza vaccine responses in males and females
Potluri T. Vaccines 2019
Adult females developed greater IL-6
and antibody responses than either
adult males or aged females
Female antibody responses
positively associated with
concentrations of estradiol.

7.500-8.000 personas en
España
0
5
10
15
20
25
2005 2010 2015 2020 2025 2030 2035 2040 2045 2050
Incidencia(miles)
Año
Incidencia estimada de la IPF en los EE.UU.2
Fernández Perez ER,. Chest 2010 ; .Gribbin J. Thorax 2006
Fibrosi pulmonar idiopàtica
• Prevalencia: Variable. Afecta más a hombres que mujeres
– 13/100.000 en mujeres
– 20/100.000 en hombres
• Se prevé que el número de nuevos casos de IPF aumentará con el
tiempo a causa del envejecimiento de la población

Impact of Sex in dyspnea in IPF
Han MK. Gender influences health-related Quality of Life in IPF. Resp Med 2010

Higher Lung Cancer Incidence in Young Women
Than Young Men in the United States
• Over the past two decades, the age-specific
incidence of lung cancer has generally decreased
among both men and women 30 to 54 years of
age in all races and ethnic groups, but the
declines among men have been steeper
• Among non-Hispanic whites, the female-to-male
incidence rate ratios increased
• Future studies are needed to identify reasons for
the higher incidence of lung cancer among young
women
Jemal A. .NEJM 2018

Rehabilitació en SAHS
• Guimaraes KC. Effects of Oropharyngeal Exercises
on Patients with Moderate Obstructive Sleep
Apnea Syndrome. Am J Respir Crit Care Med 2009
• Verma RK. Oropharyngeal exercises in the
treatment of obstructive sleep apnoea: our
experience. Sleep Breath 2016
• Diaféria G. Myofunctional therapy improves
adherence to continuous positive airway pressure
treatment. Sleep Breath 2017
• de Felício CM. Obstructive sleep apnea: focus on
myofunctional therapy. Nature and Science of
Sleep 2018

Sex differences in mandibular repositioning device
therapy effectiveness in patients with OSAS
Vechierini MF. Sleep and Breathing 2019
Mandibular repositioning device efficacy in men and women at 3- to 6-month
follow-up. AHI apnea-hypopnea index, Success rate percentage of patients with
a ≥ 50% decrease in AHI from baseline to follow-up

Impact of Gender on Incident Diabetes Mellitus
in Obstructive Sleep Apnea: A 16-Year Follow-Up
• In a multivariate analysis, DM was
predicted by OSA in women with an odds
ratio (OR) of 11.8, but not by age, body
mass index (BMI) at baseline, or weight
change at follow-up. In men, only BMI (OR
1.16) predicted DM.
Celen YT. J Clin Sleep Med 2010

Sex Differences in the Association Between Smoking
and Sleep-Disordered Breathing in the Hispanic
Community Health Study/Study of Latinos
• A total of 13,863 US Hispanic/Latino subjects,
18 to 76 years old, provided smoking histories
and underwent home SDB testing
• Sex- and age-stratified analyses were
performed
• Significant association between smoking and
SDB in younger (35-54 years old) female
smokers.
Cohen O .Chest 2019

Idiopathic environmental intolerance (IEI)
 Nonspecific symptoms when exposed to low levels of
chemicals, biologic or physical agents
 Medical societies scepticism: psychiatric disorder?
 No consistent objective diagnostic tests to define an illness...
 Cough is the most frequently reported respiratory symptom
 Psychological approach mandatory: mind & body interventions
 Quick Environmental Exposure & Sensitivity Inventory (QUEESI
questionnaire): TILT test (Toxicant-induced loss of tolerance)
Multiple Chemical Sensitivity
Black DW. Idiopathic environmental intolerance. UpToDate 2019
Roig J. Respiratory disease caused by aerotoxic syndrome. Intern Air Cabin Conference Proceed 2019
Rossi S. Multiple chemical sensitivity. State of the Art. JOEM 2018

Gender & cough
Tomljenovic D. Females have stronger neurogenic
response than males after non-specific nasal
challenge in patients with seasonal allergic rhinitis.
Med Hyp 2018
Sex differences
in cough reflex.
Plevkova J. 2017

Gender differences in the effect of urge-to-cough and
dyspnea on perception of pain in healthy adults
Gui P. Physiol Rep 2014

Abbreviations: AMCC, anterior midcingulated cortex; CB, cerebellum; IFG, inferior frontal gyrus; Ins,
insula; MD, mediodorsal nucleus of the thalamus; OFC, orbitofrontal cortex; PM, premotor area; STG,
superior temporal gyrus; VPM, ventral posteriomedial nucleus of the thalamus.
Mazzone SB. Pulmonary Pharmacology & Therapeutics 2009
Mapping supramedullary pathways involved in cough using
functional brain imaging: Comparison with pain
Comparison between
BOLD signal changes
associated with
capsaicin inhalation
(green) and painful
thermal somatosensory
stimulation (blue).
Regions of overlapping
activations appear red.

Respiratory and cardiovascular responses to walking down a traffic-polluted road
compared with walking in a traffic-free area in participants aged 60 years and older
with chronic lung or heart disease and age-matched healthy controls: a randomised,
crossover study
Sinaharay R. Lancet 2018
• Participants with COPD reported more cough (odds ratio [OR]
1·95, 95% CI 0·96–3·95; p<0·1), sputum (3·15, 1·39–7·13;
p<0·05), shortness of breath (1·86, 0·97–3·57; p<0·1), and
wheeze (4·00, 1·52–10·50; p<0·05) after walking down Oxford
Street compared with Hyde Park.
• In participants with COPD, a reduction in FEV1 and FVC, and an
increase in R5–20 were associated with an increase in during-
walk exposure to NO2, ultrafine particles and PM2.5, and an
increase in PWV and augmentation index with NO2 and
ultrafine particles.
• In healthy volunteers, PWV and augmentation index were
associated both with black carbon and ultrafine particles.

Mechanistic link between diesel exhaust particles
and respiratory reflexes
Robinson LK. J Allergy Clin Immunnol 2018

Maltais F. 2014
Bui KL. 2019
Features of quadriceps dysfunction in COPD

Sex-Differences in the Pulmonary System Influence the
Integrative Response to Exercise
Dominelli PB. Exerc Sport Sci Rev 2019.

Box and whisker plot, showing individual subject data and group mean ± SE for oxygen
uptake of the respiratory muscles (V˙O2RM) as a percentage of whole-body oxygen uptake at
maximal exercise in women and men (%V˙O2max).

The relationship between work of breathing and absolute
minute ventilation (VE) during incremental cycle exercise.

• Higher histological signs of injury observed in the quadriceps muscle of female
COPD compared to those shown by men, although their levels of lung function
impairment, nutritional status, systemic inflammation, and physical activity
were similar. Moreover, this phenomenon was evident even in moderate stages
of the disease
• Lower shift toward a higher percentage of easily fatigable fibers, higher level of
muscle damage, and lower level of signs of repair than those seen in men
suggest that limb muscle training should be less intense in COPD women
• Vit D deficiency in patients with COPD was more pronounced in women than in
men and was present even in those with only moderate lung disease
• Vit D levels were associated with muscle strength in women, both in the upper
and lower limbs: vit D positively influences the maintenance of muscle mass
Sex differences in function and structure of
the quadriceps muscle in COPD patients
Ausin P. Chron Respir Dis 2017

Troosters T. Respir Research 2013
…addressing emotional and behavioral aspects of COPD may be an
effective way to increase physical activity and improve health status in the
long term.

Depression & Anxiety in COPD
Montserrat-Capdevila J. Mental disorders
in chronic obstructive pulmonary disease.
Perspect Psychiatr Care 2018
Miravitlles M. Depressive status explains a
significant amount of the variance in
COPD assessment test (CAT) scores. Int J
Chron Obstruct Pulmon Dis. 2018
Yohannes AM. Depression and anxiety in
patients with COPD. Eur Respir Rev. 2014

Self blame & catastrophizing interpretation
• Plaufcan MR. Behavioral and characterological
self-blame in chronic obstructive pulmonary
disease. J Psychosom Res 2012.
• Solomon BK. A breathlessness catastrophizing
scale for chronic obstructive pulmonary
disease. J Psychosom Res 2015.
• Livermore N. Catastrophic interpretations and
anxiety sensitivity as predictors of panic-
spectrum psychopathology in chronic
obstructive pulmonary disease. J Psychosom
Res 2012.

When analyzing individual intervention types, cognitive
behavioral therapy appeared to be effective (g = 0.39, CI = 0.15–
0.62; p = 0.001) for improving psychological outcomes.
In contrast for physical outcomes, only mind-body interventions
(e.g. mindfulness therapy, yoga, and relaxation) revealed a
statistically significant effect (g = 0.40; CI = 0.01–0.79; p = 0.042).
Physical (dyspnea + exercise capacity + fatigue + lung function)
Farver-Vestergraard I. Psychother Psychosom 2015

 Mental training to cultivate present moment awareness
 Meditation practice is the cornerstone of mindfulness
Mindfulness
Non pharmacological approach
to psychological symptoms
related to illness such as anxiety,
depression, self blame,
catastrophic interpretations…
Mind & body interventions have been useful in many
respiratory conditions

The effect of mindfulness meditation on cough
reflex sensitivity
Young EC. Thorax 2017
Changes in cough reflex
sensitivity to citric acid in
healthy volunteers for the
control, mindfulness
intervention and voluntary
cough
suppression groups. Horizontal
lines represent median values
and error bars represent the
interquartile range.

Shikhbahaer S. Science 2017
Breathing
to inspire
and arouse
A small population
of brainstem
neurons
connects breathing
behavior to brain
arousal
Breathing
control
center
neurons
that
promote
arousal
in mice
NEUROSCIENCE
Yackle K. Science 2017

The rhythmic activity of a cluster of neurons in the brainstem initiates breathing.
This cluster is composed of distinct, though intermingled, subgroups of neurons. A
small, molecularly defined neuronal subpopulation in this breathing rhythm
generator that directly projects to a brain center that plays a key role in
generalized alertness, attention, and stress. Removal of these cells did not affect
normal breathing but left the animals unusually calm. The breathing center thus
has a direct and dramatic influence on higher-order brain function.
The calming effect of breathing
Ascending neural circuit from
preBötC. Cdh9/Dbx1 preBötC
neurons provide monosynaptic
excitatory input to
noradrenergic LC neurons,
which project throughout brain
to promote arousal and active
behaviors.
Yackle K. Science 2017

Mindfulness : amplia acceptació en dones
MBSR Pres. 2018
• Cursos 17
• Asistentes 293
• Graduados 94,3%
• Mujeres 69,6%
• Edad media 43,2 a.
• Reducción del Malestar -29,4%
• GSI inicial – 70,2%
• GSI final – 49,3%
• Recomiendan 98%
MBSR Online 2017
•Cursos 12
•Asistentes 420
•Graduados 66,5%
•Mujeres 70%
• Edad media 43 a.
• Reducción del Malestar -45%
• GSI inicial – 69,6%
• GSI final – 38,2%
• Adhesión – 69%
• Satisfacción curso 8,7/10

Optimism is associated with exceptional longevity
in 2 epidemiologic cohorts of men and women
Leo LO. PNAS September 2019
Optimism is specifically related to 11 to 15%longer life span,
on average, and to greater odds of achieving “exceptional
longevity,” that is, living to the age of 85 or beyond.

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