nmdc221 session 11: respiratory system disease part i · pdf filenmdc221 session 11:...
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NMDC221 Session 11:
Respiratory System Disease
Part I
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Topic Summary
o Respiratory System Disease Part I:
• Review anatomy and physiology of the respiratory system
• Overview of principles and considerations in nutritional
management of the respiratory system
– Effects of alcohol on respiratory function
– Effects of tobacco on respiratory function
Nutritional management for smoking cessation
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Overview of the Anatomy of the
Respiratory System
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Recommended Reading
Mahan, L.K., & Raymond, J.L. (2016). Krause’s food & the
nutrition care process (14th ed.). Pp.687-8. St.
Louis, MO: Elsevier. (prescribed text).
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Respiratory System
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Respiratory System
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Respiratory System
Functions
1. Gaseous exchange: intake of Oxygen, elimination of CO2
2. Helps regulate the blood pH – by maintaining the CO2
levels
3. Contains receptors for the sense of smell
4. Filters, warms and moistens the inspired air to make it
suitable to enter the lungs.
5. Produces and modifies the speech and vocal sounds as
the air passes over the nose and vocal folds in larynx
6. Elimination of waste: excretes small amounts of ketone
bodies, volatile molecules, heat and water
(Kumar & Clark, 2009; Tortora & Derrickson, 2006)
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Overview of principles and considerations
in nutritional management of the
respiratory system
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Respiratory nutrients to consider :
Beta Carotene 15-30mg/d Activation of lymphocytes &
macrophages. Anti-oxidant
Integrity of epithelial lining of
respiratory tract. Decreases
leukotriene formation
Carrots, Capsicums, Pumpkin,
Squash, Mango, Sweet potato
Vitamin C 500mg
divided
dosages up
to 5000mg
Immune support; assist in
regulating stress response.
Berries, Broccoli, Cabbage,
Citrus, Guava, Parsley, Peppers.
Pineapple, Rosehips,
Vitamin A 1000-5000iu Epithelial lining Apricot, Carrots, Egg Yolk, Fish
Liver Oil, Green Leafy
Vegetables, Mint
Zinc 10-100mg Production of lymphocytes,
Co-factor in PGE 1
synthesis, Tissue repair and
regeneration
Beef, Ginger, Herring, Liver, Milk,
Oyster, Pumpkin & Sunflower
Seeds, Wholegrain Cereal, Yeast
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Respiratory nutrients to consider :
Vitamin E Cell Membrane
Stability, Production
of Lymphocytes
100-1000iu Almond, Beef, Corn, Egg Yolk,
Safflower & Sunflower
Seeds, Wheat Germ
Vitamin B6 Cereals, Egg yolk,
Chicken, Legumes,
Oats, Oily fish, nuts
50–150mg Co-factor in PGE synthesis
Tryptophan metabolism
Quercetin Onions 500-1500 mg Inhibitor of inflammatory
eicosanoid synthesis
Magnesium Almonds, cashews,
soy beans, green
leafy vegetables,
wholegrains
400-800mg Bronchodilator
Cofactor desaturase enzymes
Mitochondrial function
N-acetyl
cysteine
Cysteine rich foods
– garlic, Brassica
family, eggs, animal
foods
1200mg- 3000 mg Glutathione production
Mucolytic
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Respiratory nutrients to consider :
Lecithin Soy
lecithin,
egg yolk,
peanuts,
cauliflower
5-20gms daily Phospholipid component of
surfactant
Bromelain Pineapple 150-400mg Mucolytic
Anti-inflammatory
Protein digestion
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Airway Epithelium
o Maintains sterile, undamaged airway tracts via clearance
of irritants and other noxious particles
o Regulates airway physiology via production of smooth
muscle relaxant factors (PGE2, nitric oxide)
o Susceptible to damage by;
• Inhaled pollutants
• Proteases released from inflammatory cells & dust
mites
• Reactive oxygen species (ROS) from endogenous and
exogenous sources
(Zalewski et al, 2005)
Respiratory System
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Airway Epithelium
o Constant damage of mucin, growth factors, and pro-
inflammatory cytokines (TNFα)
o Airway epithelium is susceptible to apoptosis by various
stimuli including corticosteroids, pro-inflammatory
cytokines and ROS
o While beneficial in normal circumstances, excessive
apoptosis can lead to chronic inflammatory disease
o Damage to airway epithelium is significant for
development of conditions such as asthma, chronic
obstructive pulmonary disease (COPD)
(Zalewski et al, 2005)
Respiratory System
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Oxidation and the Lungs
o Directly exposed to high levels of oxygen
• Free radicals activate inflammatory cells which
generate more reactive oxygen species (ROS) and
reactive nitrogen species (RNS)
o Has to have efficient antioxidant mechanisms
o Oxidative stress/lipid peroxidation may be associated
with pulmonary narrowing in the general population
(Kinnula, 2005)
Respiratory System
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Antioxidant Defense of the Lung
(Kinnula, 2005)
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Respiratory System
Agents Antioxidant Defense of the Lung
Mucins cysteine rich glycoproteins in epithelial lining fluid
Glutathione (GSH) a primary antioxidant in the lungs
Glutathione related enzymes
GSH peroxidase
GSH reductase
involved in hydrogen peroxide decomposition.
Cofactor is selenium
Catalase For hydrogen peroxide decomposition
Metal binding proteins albumin, transferrin, ferritin, ceruloplasmin, lactoferrin,
metallothionein
Superoxide dismutase
(SOD)
act against superoxide radicals. Cofactors of manganese (Mn) and Copper (Cu) / Zinc (Zn)
Thiol-containing proteins thioredoxins etc.
(Kinnula, 2005)
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Respiratory System
Zinc
In airway inflammation:
o Zinc acts as an antioxidant to stabilize sulfhydryl and
membrane lipids and suppress nitric oxide production
o Zinc may act, similar to calcium, as second messengers
in cell signaling
o Mast cells are rich in zinc (found in granules)
(Kitajima et al. 2009)
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Respiratory System
Zinc
Mild nutritional zinc deprivation in humans has several
effects
o A decline in the ratio of CD4+/CD8+ T cells
o Diminished functional activity of the T helper1 subset but
unaffected activity of T helper2 cells, creating a Th1
deficiency and immunosuppression
o T cells are susceptible to zinc deficiency
(Kitajima et al. 2009)
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Zinc
Zinc deficiency has been associated with:
o Increased oxidative stress in the lung
o Increased apoptosis in inflamed airway epithelium
o Altered lipid composition, enzyme activity and protein
composition of plasma membranes
o Impaired fibroblast proliferation and collagen synthesis
(Kitajima et al. 2009)
Respiratory System
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Effects of Alcohol on Respiratory System
Pharmaceutical treatment for Alcohol
withdrawal
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Respiratory System
Alcohol
o Alveolar glutathione levels are decreased by 80% in
alcohol-dependent patients
o Glutathione is an important nutrient for healthy lung
function
• Helps the alveolar cells maintain antioxidant
homeostasis
• essential for the detoxification of endogenous and
exogenous oxidant radicals in the airway
o Glutathione concentration in 100x higher is the lung,
compared with plasma levels
(Brown et al, 2004)
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Respiratory System
Alcohol
The decrease in glutathione leads to several issues
o Sensitization of Type II alveolar cells to inflammatory
mediator induced apoptosis
o Delays repair to epithelium resulting in exacerbation of injury and fibrotic lesions
o Surfactant lipoproteins are converted from an active form to inactive
(Brown et al. 2004)
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Alcohol and GSH in the Lungs
(Brown et al. 2004)
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Respiratory System
Alcohol
Alcohol also has a detrimental effect on immunity
o Reduced macrophage ability to phagocytose and fully
encapsulate bacteria from the airways
o Impaired release of pro-inflammatory cytokines,
chemokines and oxidant radicals required for microbial
killing
o When pro-cysteine was added to the diet, macrophage
phagocytosis was maintained at control values
(Brown et al. 2004)
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Respiratory System
Drug Action Side Effects Interaction
Aldehyde
Dehydrogenase
Inhibitor:
Disulfiram
Inhibits aldehyde
dehydrogenase
If alcohol is consumed
sensations of severe
vasodilation, headache,
shortness of breath,
nausea, vomiting,
dizziness, confusion &
chest pains lasting for
several hours.
None listed
Acamprosate Reduces glutamate &
increases GABA in CNS.
Reduces cravings for
alcohol & symptoms of
alcohol withdrawal
GIT symptoms & skin
rash
None listed
(Bullock et.al, 2007; Bryant & Knights, 2011, p. 424)
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Respiratory System
Drug Action Side Effects Interaction
Dopamine
Receptor
Antagonist:
Thioridazine
Antagonizes
dopamine D2
receptors,
dopamine
levels increase
enhancing the
CNS inhibitory
effects. This
has been found
to reduce the
cravings for
alcohol.
Extrapyramid
al effects:
sedation,
alteration to
the CNS
regulation of
motor co-
ordination.
Co-enzyme Q10: inhibits enzymes
containing CoQ10.
Phenylalanine: Exacerbate tardive
dyskinesia symptoms Avoid
Potassium: reduce severity of
ventricular arrhythmias (drug side
effect)
Vitamin A: elevated. Monitor for
toxicity signs
Vitamin B3: increases the efficacy of
the drug. stimulating GABA receptors
without attaching to the receptor sites
Vitamin D: CYP2D6 inhibitor reducing
metabolism & breakdown of the drug.
(Harkness &Bratman, 2003; Bryant & Knights, 2007; Bullock et.al. 2007; Stargrove et.al. 2008)
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Respiratory System
Drug Action Side Effects Interactions
Opioid Antagonist:
Naltrexone
Reduces the
cravings for alcohol
and alters the
euphoric effect
when alcohol is
consumed.
Transient post
therapy symptoms
include fatigue,
insomnia,
headache,
dizziness & nausea.
Rarely
hepatotoxicity can
occur.
None listed
(Harkness &Bratman, 2003; Bryant & Knights, 2007; Bullock et.al. 2007; Stargrove et.al. 2008)
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Effects of tobacco smoking on
respiratory function
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Smoking still causes a higher burden of disease than any other
behavioural risk factor, representing 9.6% of the total burden in men and
5.8% in women (RACGP 2014).
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Smoking
Smoking Chemicals
Tobacco smoke contains many chemicals that have a direct
effect on respiratory health
o Nicotine: increases platelet aggregation
o Carbon monoxide: impaired oxygen transportation
o Nitrogen oxides: lung damage related to emphysema
o Hydrogen cyanide: damaging effect to cilia
o Metals: carcinogenic
o Radioactive compounds: carcinogenic
(Scollo & Winstanley, 2010)
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Inflammation
o Cigarette smoke contains high levels of oxygen and nitric
oxide
o Exposure to cigarette smoke leads to an immediate
transient oxidant burden
o Typical features of smoker’s lungs:
• Inflammation with recruitment of neutrophils and
macrophages into the airways
• Small airway obstruction/fibrosis
• Destructive processes in the parenchyma
(Kinnula, 2005)
Smoking
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Antioxidants
o Antioxidant enzymes induced by cigarette smoke
• Manganese superoxide dismutase (MnSOD)
• GSH associated enzymes
o Induction of antioxidant enzymes is transient, during
severe/and or chronic exposure, these enzymes may be
down-regulated
(Kinnula, 2005)
Smoking
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Smoking
Nutritional Deficiencies
o A Bangladeshi study found that smokers had lower
levels of serum vitamin C and copper, and lower zinc
intakes than non-smokers (Faruque et al, 1995)
o Levels of carotenoids were examined and smokers were
found to have 21-29% lower levels of α-carotene, β-
carotene, cryptoxanthin and lycopene compared with
non-smokers (Pamuk et al, 1994)
o In another study, smokers were found to have lower
levels of selenium, as well as vitamin C and β-carotene,
than non-smokers (Galan et al, 2005)
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Smoking
Therapeutic Actions
Vitamin C
o Vitamin C levels are significantly affected by smoking. A
study found that smokers had a 24% lower serum
vitamin C. In addition to this, smokers consumed 20%
less vitamin C from dietary sources
(Schectman, Byrd & Gruchow, 1989)
o Free radicals produced by smoking have a negative
effect on the endothelium. An infusion of 1 gram of
vitamin C was found to attenuate this dysfunction,
leading to better vasodilation
(Heitzer, Just & Munzel, 1996)
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Smoking
Therapeutic Actions
β-carotene
o Supplemental β-carotene has recently been linked to
increased rates of lung cancer in smokers. It is thought
that this is due to a proxidant effect
(Arora, Willhite & Liebler, 2001)
o Scientists are looking to test this effect further, but as yet
there is no conclusive evidence about the safety of β-
carotene supplements in smokers
o Nutritional clinical protocols would suggest that
increasing dietary sources of carotenoids would be a
judicious way forward
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Smoking
Cadmium
o Smoking is a major cause of cadmium intake. The
cadmium in cigarettes is highly bioavailable. Smokers
have a 4-5 times higher blood cadmium that non-
smokers (Satarug & Moore, 2004)
o Cadmium leads to several health effects: renal disease,
bone fragility, pre-term delivery and low birth weight and
cancer (Satarug & Moore, 2004)
o Vitamin C, zinc, lipoic acid, selenium, and glutathione
are all useful antagonists to cadmium (Osiecki, 2006)
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Smoking:
Vitamin C 500-5,000mg Supports immune responses, antioxidant, reduces
inflammation, maintains integrity of collagen structures within
the lungs.
Vitamin E 100-1000iu Cell Membrane Stability, Production of Lymphocytes
Zinc 10-100mg Production of Lymphocytes, Co-factor in PGE 1 synthesis,
Tissue repair and regeneration
Lipoic acid 100-600mg Scavenges peroxynitrite free radicals, recycles other
antioxidant nutrients
Selenium 50-200mcg Free radical scavenger, modulates immune responses
Carotenoids Increase in
diet only
Increases cell mediated immunity, antioxidant, maintains lining
of lungs, reduces
(Coulston et al 2001; Osiecki, 2006; Sarris & Wardle, 2010)
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Smoking Cessation
and
Pharmaceutical treatment for nicotine
withdrawal
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Smoking cessation interventionso Brief interventions for smoking cessation involve
opportunistic advice, encouragement and referral.
Interventions should include one or more of the
following:
• brief advice to stop smoking
• an assessment of the smoker’s interest in quitting
• an offer of pharmacotherapy where appropriate
• providing self-help material
• offering counselling within the practice or referral to external
support such as
– Quit line an accredited tobacco treatment specialist
or other
– local programs in your area (RACGP 2014).
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The 5 A’s - ask, assess, advise,
assist and arrange follow-up
Evidence based approach Royal Australian College of General Practitioners, 2014
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Ask
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Assess
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Advise
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Assist
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Nicotine addiction
o Most smokers use tobacco despite the known harmful effects as
they find it difficult to quit.
o However most smokers want to reduce or stop smoking.
o More than 85 percent of those who try to quit on their own relapse,
most within a week.
o That said, repeated attempts that may take months to years is
usually successful.
o The addictive nature of nicotine is associated with activation of the
reward circuitry and increases in dopamine.
• Peak levels of nicotine reach the brain 10 seconds after inhalation.
• However, the acute effects of nicotine dissipate quickly, as do the associated
feelings of reward, which causes the smoker to continue dosing to maintain the
drug’s pleasurable effects and prevent withdrawal (National Institute on Drug
Abuse 2014).
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Glutamine
o GLN attenuated the lung histopathological alterations,
improved pulmonary oxygenation, and mitigated
pulmonary oedema in rats. GLN mitigated smoke
inhalation-induced excessive collagen deposition and
mitigated smoke inhalation-induced lung inflammatory
response, and further prevented the activity of NF-
kappa-B. GLN protected rats against smoke inhalation-
induced lung injury and its protective mechanism seems
to involve in inhibition inflammatory response and
enhancing HSP expression (Li et al 2013).
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N-Acetyl Cysteine (NAC)
Varenicline (Champix) has demonstrated superior
efficacy over other smoking cessation
pharmacotherapies, though 50-60% of those treated do
maintain abstinence. Some preclinical findings suggest
that new nicotine dependence pharmacotherapies
should target the glutamatergic system, given its
demonstrated role in addiction. Attention has been
given to N-acetylcysteine (NAC), which appears to
restore normal glutamate signalling in animal models
(McClure et al 2014) .
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NAC Open label trial
o Participants (n = 19) were daily cigarette smokers, they received 4
weeks of open-label treatment with NAC (1200 mg twice daily) and
Varenicline VAR (1 mg twice daily, following titration) and were
assessed weekly for adverse events (AEs), smoking, craving and
withdrawal. Results: Sixteen participants reported a total of 40 AEs,
and most were mild (88%). The most commonly reported AE was
nausea (15%). Medication adherence, assessed via self-reports and
pill counts, was excellent (98%). Exploratory analyses showed
reductions in cigarettes per day
o Conclusions: These preliminary data provide the first
demonstration of safety and feasibility of the co-administration of
NAC and VAR in cigarette smokers (McClure et al 2014) .
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Traditional Remedy – mucolytic and
facilitates expectoration
o 5 grams of organic lecithin granules mixed with one
clove of crushed garlic.
o This can be taken off the spoon or encapsulated as
required. This can be taken three times daily in acute or
chronic bronchial infections and/or to facilitate
expectoration.
o Synergistic mix of phospholipids that improve lung
compliance (surfactant) whilst aiding absorption of
volatile compounds in garlic. Garlic has antimicrobial
effects and also high in cysteine, thereby providing
further explanation of synergistic effects.
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Class Discussiono Case study:
o Female 38 years has been smoking 10-20 cigarettes per day for 20
years. Consumes one glass of white wine most evening.
o She comes to visit you to stop smoking. She has tried several times
over the past years. Her longest period without is 4 months.
o Her BMI is 21, she reports bronchitis at least once each winter and
she has a reduced sense of smell, and mild depression and low
level anxiety. She feel the smoking helps with this. Otherwise her
health is good. Her diet consists of good quality protein, fruits and
vegetables and limited junk food.
o TASK
o Please make dietary and nutrient recommendations including
rationale and dosages to support her desire to stop smoking.
Consider both short term and long term goals and treatment
strategy.
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Smoking
Drug Action Side Effects Interactions
Nicotine
Replacement
Therapy – gum,
patches, microtabs,
lozenges, inhalers.
E-cigarettes
In a withdrawal
situation, nicotine
replacement
therapy delivers a
low dose of nicotine
to the nicotinic
receptors located in
the CNS & skeletal
muscles.
Increased heartbeat,
increased GIT motility
(diarrhoea, vomiting),
increased muscle
tension, headache,
insomnia.
Delivery systems can
cause localised irritation
– mouth mucous
membranes or skin
irritation.
None listed
(Bryant & Knights, 2007; Bullock et.al. 2009)
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Smoking
Drug Action Side Effects Interactions
Bupropion
(Zyban)
Increases dopamine levels in
the nucleus accumbens area of
the brain. This area is
responsible for feelings of
reward and addictive
behaviour. Bupropion is also a
nicotinic receptor antagonist.
Agitation,
tremor.
Nausea,
constipation.
Headache,
insomnia.
None Listed
Varenicline
(Champix)
Block nicotinic receptors
preventing nicotine stimulation
of dopamine release.
Research has found Champix
to be more effective than
Zyban.
Nausea, dry
mouth,
headache,
dizziness, sleep
disturbance and
tiredness.
None Listed,
NAC has a positive
effect
(Berrettini & Lerman, 2005; Bullock et.al. 2007; Bryant & Knights, 2009)
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© Endeavour College of Natural Health endeavour.edu.au 57
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