Respiratory DiseaseRespiratory Disease

Obstructive & Restrictive Obstructive & Restrictive Pulmonary Diseases Pulmonary Diseases

LUNG STRUCTURE

Obstructive Pulmonary Obstructive Pulmonary DiseaseDisease

Indicate obstruction to Indicate obstruction to flow of air flow of air through the through the airways.airways.

As asthma , COPD ( chronic bronchitis & As asthma , COPD ( chronic bronchitis & emphysema ) , Bronchiactasis , cystic fibrosis…emphysema ) , Bronchiactasis , cystic fibrosis…

TLC ( total lung capacity ) increaseTLC ( total lung capacity ) increase

RV ( residual volume ) increaseRV ( residual volume ) increase

FEV1 / VC less than 70%FEV1 / VC less than 70%

Restrictive Pulmonary Restrictive Pulmonary DiseaseDisease

Indicate limitation to full Indicate limitation to full expantionexpantion of the lungs of the lungs because of diseases in the lung because of diseases in the lung paranchyma paranchyma , chest , chest wall or diaphragm.wall or diaphragm.

( Lung volumes are decrease but flow rates are normal ( Lung volumes are decrease but flow rates are normal ).).

As As Interstitial lung diseaseInterstitial lung disease( cryptogenic fibsosing ( cryptogenic fibsosing alveolitis , sarcoidosis, asbestosis, silicosis , coal alveolitis , sarcoidosis, asbestosis, silicosis , coal worker pneumoconiosis…) worker pneumoconiosis…)

TLC ( total lung capacity ) decreaseTLC ( total lung capacity ) decrease

RV ( residual volume ) decreaseRV ( residual volume ) decrease

FEV1 / VC = or more than 70%FEV1 / VC = or more than 70%

Pulmonary function testPulmonary function test

Lung volumesLung volumes TLCTLC ( total lung capacity ): is the volume of gas ( total lung capacity ): is the volume of gas

contained in the lungs after a maximal contained in the lungs after a maximal inspiration.inspiration.

RVRV ( residual volume ): is the volume of gas ( residual volume ): is the volume of gas remaining in the lungs at the end of a maximal remaining in the lungs at the end of a maximal expiration.expiration.

VCVC ( vital capacity ): is the volume of gas that ( vital capacity ): is the volume of gas that exhaled from the lungs during expiration.exhaled from the lungs during expiration.

TLC = VC + RVTLC = VC + RV

Lung volumes are Lung volumes are increase increase in obstructive lung in obstructive lung diseases.diseases.

Lung volumes are Lung volumes are decrease decrease in restrictive lung in restrictive lung diseases.diseases.

Gas flow rateGas flow rate FEV1FEV1( forced expiratory volume in the first second ( forced expiratory volume in the first second

):):

is the volume of gas exhaled during the first second is the volume of gas exhaled during the first second

of expirationof expiration..

FVCFVC ( forced vital capacity ):( forced vital capacity ):

is the total volume of gas that exhaled from the lungs is the total volume of gas that exhaled from the lungs during expiration.during expiration.

Flow rate Flow rate decreasedecrease in obstruction to air in obstruction to air flow( obstructive lung disease ) flow( obstructive lung disease )

FEV1 / VC FEV1 / VC less than 70% less than 70% ( in ( in ObstructiveObstructive lung diseases ). lung diseases ).

FEV1 / VC FEV1 / VC = or more than 70%= or more than 70%(in (in RestrictiveRestrictive lung lung diseases).diseases).

Obstructive Pulmonary Obstructive Pulmonary DiseaseDisease

ASTHMAASTHMA

What is Asthma?What is Asthma? Chronic disease of the airways that may causeChronic disease of the airways that may cause

WheezingWheezing BreathlessnessBreathlessness Chest tightnessChest tightness Nighttime or early morning coughingNighttime or early morning coughing

Episodes are usually associated with Episodes are usually associated with widespread, but variable, airflow obstruction widespread, but variable, airflow obstruction within the lung that is often reversible either within the lung that is often reversible either spontaneously or with treatment.spontaneously or with treatment.

Bronchial asthmaBronchial asthma

DefinitionDefinition It's paroxysmal reversible airway obstructionIt's paroxysmal reversible airway obstruction

characterized by airway inflammation & characterized by airway inflammation & increased airway responsiveness to stimuli increased airway responsiveness to stimuli resulting in symptoms of resulting in symptoms of wheezewheeze , ,cough cough ,,dyspnoea dyspnoea && chest tightness chest tightness . .

Functionally characterized by airway obstruction Functionally characterized by airway obstruction which is variable over short periods of time or is which is variable over short periods of time or is reversiblereversible with treatment ( the airway obstruction with treatment ( the airway obstruction may be relieved spontaneously or with may be relieved spontaneously or with therapy ) .therapy ) .

Increased responsiveness of the airways & Increased responsiveness of the airways & reversable airflow obstruction are not unique to reversable airflow obstruction are not unique to asthma .asthma .

Many patients with COPD exhibit nonspecific Many patients with COPD exhibit nonspecific hyperresponsiveness, although obstruction is not hyperresponsiveness, although obstruction is not completely reversible( partially reversible ) .completely reversible( partially reversible ) .

Asthmatic Bronchitis :Asthmatic Bronchitis : some current or some current or past cigarette smokers with chronic bronchitis & past cigarette smokers with chronic bronchitis & airflow obstruction exhibit episodic wheezing & airflow obstruction exhibit episodic wheezing & SOB that closely mimic asthma.( a subcategory of SOB that closely mimic asthma.( a subcategory of chronic bronchitis that has features in common chronic bronchitis that has features in common with asthma ) .with asthma ) .

– In persons older than 40 years who were newly In persons older than 40 years who were newly diagnosed as having asthma , approximately one diagnosed as having asthma , approximately one half had a history of cigarette smoking & had been half had a history of cigarette smoking & had been previously diagnosed as having chronic bronchitis & previously diagnosed as having chronic bronchitis & emphysema ,these patients would have been more emphysema ,these patients would have been more accurately diagnosed as having accurately diagnosed as having Asthmatic Asthmatic Bronchitis.Bronchitis.

In persons older than 40 years with features of asthma In persons older than 40 years with features of asthma who have never smoked cigarettes called who have never smoked cigarettes called adult – adult – onset asthmaonset asthma..

Prevalence of asthma sssss: Asthma is very commen ,about 4-5%of population have Asthma is very commen ,about 4-5%of population have

bronchial asthma .bronchial asthma .

The prevalence of asthma increased in the last century .The prevalence of asthma increased in the last century . About 300 million people world-wide suffer from asthma About 300 million people world-wide suffer from asthma

,, and an additional 100 million may be diagnosed with and an additional 100 million may be diagnosed with

asthma by 2025 .asthma by 2025 .

Asthma occur in all ages but predominantly in early life Asthma occur in all ages but predominantly in early life ( more common in children ) .( more common in children ) .

In childhood , asthma is more common in boys In childhood , asthma is more common in boys (male :female 2:1), but following puberty females are (male :female 2:1), but following puberty females are more frequently affected (sex ratio equilized by the age more frequently affected (sex ratio equilized by the age of 30) .of 30) .

Asthma prevalence is higher amongAsthma prevalence is higher among– children than adultschildren than adults

– boys than girlsboys than girls

– women than menwomen than men

are likely to have asthma.*

On average, 3 children in a classroom of 30

Aetiology of asthma :Aetiology of asthma :

The aetiology of asthma is complex The aetiology of asthma is complex and multiple and multiple environmental environmental & & genetic genetic factors are implicated .factors are implicated .

There are There are genetic markersgenetic markers on on multiple chromosomes that relate to multiple chromosomes that relate to bronchial hyperresponsiveness & bronchial hyperresponsiveness & atopy. atopy.

Risk Factors for Developing AsthmaRisk Factors for Developing Asthma

Genetic characteristicsGenetic characteristics Occupational exposures Occupational exposures Environmental exposuresEnvironmental exposures

Factors may predispose to Factors may predispose to asthmaasthma : :

- Childhood - Childhood infectioninfection eg.: eg.: respiratory syncytial respiratory syncytial virusvirus . .

In patients with chronic asthma In patients with chronic asthma MycoplasmaMycoplasma & & ChlamydiaChlamydia species have been identified in lung species have been identified in lung specimens , suggesting a possible role of specimens , suggesting a possible role of infection in the pathogenesis .infection in the pathogenesis .

--Allergen exposureAllergen exposure eg.: house dust mite . eg.: house dust mite .

-Indoor pollution-Indoor pollution, warm, humid, centrally heated , warm, humid, centrally heated homes.homes.

-Dietary -Dietary deficiency of antioxidantsdeficiency of antioxidants . .

-Exposure to -Exposure to petspets in early life . in early life .

-Obesity-Obesity (gastroesophegeal reflux) . (gastroesophegeal reflux) .

Factors may protect against Factors may protect against asthma :asthma :

--Living on farmLiving on farm ( childhood exposure to antigen ( childhood exposure to antigen –rich environment is associated with a redused –rich environment is associated with a redused incidence of asthma & allergy by changes in the incidence of asthma & allergy by changes in the maturation process of the immune system.).maturation process of the immune system.).

-predominance of -predominance of lactobacilli lactobacilli in gut flora .in gut flora .

--Milk & antioxidantsMilk & antioxidants such as vit. E. such as vit. E.

*According to the aetiology , we can divide *According to the aetiology , we can divide asthma in to :asthma in to :

Allergic asthmaAllergic asthma : Atopy is the single : Atopy is the single largest risk factor for the development of largest risk factor for the development of asthma ,personal or family history of asthma ,personal or family history of allergy ,increase IgE level ,positive skin allergy ,increase IgE level ,positive skin reaction to intradermal injection of extracts reaction to intradermal injection of extracts antigens .antigens .

Idiosyncratic asthmaIdiosyncratic asthma : Non atopic ,no : Non atopic ,no personal or family history of allergy .personal or family history of allergy .

**Onset in early lifeOnset in early life : Strong allergic : Strong allergic components .components .

* * Onset in late lifeOnset in late life : non allergic or have a : non allergic or have a mixed aetiology .mixed aetiology .

Pathophysiology of asthma :Pathophysiology of asthma :

Asthma is multifactorial in origin arising Asthma is multifactorial in origin arising from interaction of both genetic & from interaction of both genetic & environmental factors .environmental factors .

Airway inflammation occurs when Airway inflammation occurs when genetically susceptible individuals are genetically susceptible individuals are exposed to environmental factors .exposed to environmental factors .

*Cardinal pathophisiological features of asthma:*Cardinal pathophisiological features of asthma:

1-Airwflow limitation:1-Airwflow limitation: usually usually reversereverse spontaneously or with treatment. spontaneously or with treatment.

2-Airway hyper-responsiveness2-Airway hyper-responsiveness: : Exaggerated Exaggerated bronchoconstrictionbronchoconstriction to a wide range of to a wide range of

stimuli eg.: exercise, cold air…..stimuli eg.: exercise, cold air…..

3-Airway inflammation3-Airway inflammation : : Antigen-antibody reaction occur & leads to an Antigen-antibody reaction occur & leads to an

inflammatory reaction in which several different cells inflammatory reaction in which several different cells are involved namely mast cells, macrophages & are involved namely mast cells, macrophages & oesinophils which produce mediators such as oesinophils which produce mediators such as histamine,histamine, prostaglandin prostaglandin & l& leukotriens eukotriens ..

These mediators (These mediators (histamine,histamine, prostaglandin prostaglandin & & lleukotriens )eukotriens )

interact in a complex way resulting in interact in a complex way resulting in bronchial bronchial hyperresponsivenesshyperresponsiveness which cause the following which cause the following pathological changes in asthma :pathological changes in asthma :

1.1. -Bronchial muscle spasm, smooth muscle -Bronchial muscle spasm, smooth muscle hypertrophy & hyperplasia .hypertrophy & hyperplasia .

2.2. -Mucosal swelling (oedema ). -Mucosal swelling (oedema ). 3.3. -Hyperplasia of mucous glands with mucous plugging -Hyperplasia of mucous glands with mucous plugging

(viscid secretion ).(viscid secretion ).4.4. -Thickened basement membrane .-Thickened basement membrane .5.5. -Epithelial damage .-Epithelial damage .6.6. -vasodilatation .-vasodilatation .

All these lead to airway obstruction, that is why All these lead to airway obstruction, that is why asthma is not only asthma is not only bronchconstriction bronchconstriction ,but also ,but also associated with associated with inflammatory reaction.inflammatory reaction.

Pathology of AsthmaPathology of Asthma

Source: “What You and Your Family Can Do About Asthma” by the Global Initiative For Asthma Created and funded by NIH/NHLBI, 1995

Normal Asthma

Asthma involves inflammation of the airways

With increasing severity & chronicity of With increasing severity & chronicity of asthmaasthma

remodelling of the airways occur leading to remodelling of the airways occur leading to fibrosisfibrosis of the airway wall,of the airway wall, fixed narrowingfixed narrowing of the airways & a reduced response to of the airways & a reduced response to bronchodilator medications . bronchodilator medications .

Pathogenesis of allergic asthma:Pathogenesis of allergic asthma:

Inhaled antigen is processed by Inhaled antigen is processed by mucosal dendritic cellsmucosal dendritic cells & & presented to presented to Tho-T cellsTho-T cells. This results in the generation of either . This results in the generation of either Th1 Th1 or or Th2 Th2 – T cells. With – T cells. With Th2 predominating in asthmaTh2 predominating in asthma . .

Th2-T cells produces Interleukins Th2-T cells produces Interleukins IL-4, IL-6IL-4, IL-6 & & IL-13 IL-13 which which stimulate stimulate B-cells B-cells to produce to produce IgEIgE , which binds to , which binds to mast cellsmast cells..(IgE also bind to basophils & other cells.).(IgE also bind to basophils & other cells.).

Inhaled antigen binds to IgE , stimulating the Inhaled antigen binds to IgE , stimulating the mast cellmast cell to to degranulate , which in turn leads to the release of mediators of degranulate , which in turn leads to the release of mediators of the immediate response & the late resonse ( mediators like the immediate response & the late resonse ( mediators like Histamine & Leukotrienes ). Histamine & Leukotrienes ).

Histamine & LeukotrienesHistamine & Leukotrienes produce produce bronchospasm & airway bronchospasm & airway oedema.oedema.

Released chemotactic factors, along with factors Released chemotactic factors, along with factors from Th2 T-cells ( from Th2 T-cells ( IL-3 , IL-5 & GM-CSFIL-3 , IL-5 & GM-CSF “ “ Granulocyte-Macrophage –colony – stimulating Granulocyte-Macrophage –colony – stimulating factor” ) facilitate factor” ) facilitate eosinophil eosinophil traffic from the traffic from the bone marrow to the airway walls. bone marrow to the airway walls.

These late responses lead to : excessive mucous These late responses lead to : excessive mucous production , airway wall inflammation & production , airway wall inflammation & hyperresponsiveness. hyperresponsiveness.