NMDC221 Session 11: Respiratory System Disease Part I · PDF fileNMDC221 Session 11:...

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NMDC221 Session 11:

Respiratory System Disease

Part I


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


Overview of the Anatomy of the

Respiratory System


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).


Respiratory System


Respiratory System


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)


Overview of principles and considerations

in nutritional management of the

respiratory system


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



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



Lecithin Soy

lecithin,

egg yolk,

peanuts,

cauliflower

5-20gms daily Phospholipid component of

surfactant

Bromelain Pineapple 150-400mg Mucolytic

Anti-inflammatory

Protein digestion


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


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


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


Antioxidant Defense of the Lung

(Kinnula, 2005)


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)


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)


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



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


Respiratory System


Effects of Alcohol on Respiratory System

Pharmaceutical treatment for Alcohol

withdrawal


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)


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)


Alcohol and GSH in the Lungs

(Brown et al. 2004)


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)


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)


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)


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)


Effects of tobacco smoking on

respiratory function


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).


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)


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


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


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)


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)


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


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)


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)


Smoking Cessation

and

Pharmaceutical treatment for nicotine

withdrawal


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).


The 5 A’s - ask, assess, advise,

assist and arrange follow-up

Evidence based approach Royal Australian College of General Practitioners, 2014


Ask


Assess


Advise


Assist


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).


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).


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) .


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) .


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.


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.


Smoking


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)


Smoking


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)


ReferencesArora, A., Willhite, C., & Liebler, D. (2001). Interactions of β-carotene and

cigarette smoke in human bronchial epithelial cells. Carcinogenesis,22(8), 1173-1178. doi: https://doi.org/10.1093/carcin/22.8.1173

Berrettini, W. H., & Lerman, C. E. (2005). Pharmacotherapy and pharmacogenetics of nicotine dependence. American journal of psychiatry. 162(8), 1441-1451. Retrieved from http://www.ebscohost.com

Brown, L. S., Harris, F. L., Ping, X., & Gauthier, T. W. (2004). Chronic ethanol ingestion and the risk of acute lung injury: a role for glutathione availability?. Alcohol, 33(3), 191-197. Retrieved from http://www.ebscohost.com

Bryant, B. J., & Knights, K. M. (2015). Pharmacology for health professionals

(4th ed.). Chatswood, NSW: Elsevier.

Bullock, S., & Manias, E. (2017). Fundamentals of pharmacology (8th edition).

Melbourne, Vic: Pearson Australia.

Coulston, A., & Boushey, C. (2001). Nutrition in the prevention and treatment of disease. London, England: Academic Press.

Faruque, M. O., Khan, M. R., Rahman, M. M., & Ahmed, F. (1995). Relationship between smoking and antioxidant nutrient status. The British Journal Of Nutrition, 73(4), 625-632. Retrieved from http://www.ebscohost.com


ReferencesGalan, P., Viteri, F. E., Bertrais, S., Czernichow, S., Faure, H., Arnaud, J., ...

Hercberg, S. (2005). Serum concentrations of β-carotene, vitamins C and E, zinc and selenium are influenced by sex, age, diet, smoking status, alcohol consumption and corpulence in a general French adult population. European Journal of Clinical Nutrition, 59(10), 1181-1190. doi:10.1038/sj.ejcn.1602230

Harkness, R., & Bratman, S. (2003). Mosby’s handbook of drug-herb and drug-supplement interactions. St. Louis, MO: Mosby.

Heitzer, T., Just, H., & Münzel, T. (1996). Antioxidant vitamin C improves endothelial dysfunction in chronic smokers. Circulation, 94(1), 6-9. Retrieved from http://www.ebscohost.com

Kinnula, V. L. (2005). Focus on antioxidant enzymes and antioxidant strategies in smoking related airway diseases. Thorax, 60(8), 693-700. Retrieved from http://www.ebscohost.com

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Saunders Elsevier.

Li, W., Qiu, X., Wang, J., Li, H., Sun, Y., Zhang, F., & ... Xia, Z. (2013). The

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doi:10.1016/j.intimp.2013.02.022.


ReferencesMcClure, E. A., Baker, N. L., Gipson, C. D., Carpenter, M. J., Roper, A. P.,

Froeliger, B. E., & ... Gray, K. M. (2015). An open-label pilot trial of N-

acetylcysteine and varenicline in adult cigarette smokers. The

American Journal of Drug And Alcohol Abuse, 41(1), 52-56.

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National Institute for Drug Abuse. (2014). Is nicotine addictive? Retrieved from

http://www.drugabuse.gov/publications/research-

reports/tobacco/nicotine-addictive

Pamuk, E. R., Byers, T., Coates, R. J., Vann, J. W., Sowell, A. L., Gunter, E. W.,

& Glass, D. (1994). Effect of smoking on serum nutrient

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Pizzorno, J. E., & Murray, M. T. (2006). Textbook of natural medicine. St. Louis,

Mo: Churchill Livingstone/Elsevier.

RACGP. (2013). Supporting smoking cessation: A guide for health

professionals. Retrieved from

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cessation.pdf


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