PFT andInterstitial lung diseases

Presenter Dr.CHAKRADHAR

Physiology of Breathing • inspiration-it is an active process, due to

contraction of diaphragm ,intercostals intrathoracic volume increases resulting in fall of intrapleural pressure from -2.5mmhg to -6 mmhg .this stretches the lung resulting in its expansion and inflow of air

• expiration – quite expiration at rest is a passive process while forceful expiration is an active process during quite expiration increase in intra alveolar pressure is due to relaxation of diaphragm ,elastic recoil of lung tissue ,surface tension due to air fluid interaction in alveoli

• Lung properties that determine lung volumes and capacities

Static property compliance/ elastic recoil

Dynamic property airway resistance

Compliance described as dispensability of the lungIt is defined by amount of volume change per unit

change in pressure over pressure volume curvesIt depends on elastic property of lung tissue and

surface tension

Decreased compliance in fibrosis increased compliance in emphysema

Effect of elastic property on compliance

In normal lung compliance is more during expiration than in inspiration this difference is called hysteresis it occurs due to presence of surfactant-ganong

Normal lung

hysteresis

Effect of surface tension on compliance

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Volumes

Residual volume(RV)Volume of air remaining in the lungs after maximalexpiration

Expiratory reserve volume(ERV) Maximal volume of air expired from the restingend-expiratory level

Tidal volume(TV)Volume of air inspired or expired with each breath duringquiet breathing

Inspiratory reserve volume(IRV)Maximal volume of air inspired from the restingend-inspiratory level

CAPACITIES

Inspiratory capacity(IC)Maximal volume of air inspired from the end-expiratorylevel (the sum of IRV and TV)

Vital capacity(VC) Maximal volume of air expired form the maximalinspiratory level

Inspiratory vital capacity(IVC) Maximal volume of air inspired form the maximalexpiratory level

Functional residual capacity(FRC)Volume of air remaining in the lungs at the end-expiratorylevel (the sum of RV and ERV)

Total lung capacity(TLC)Volume of air in the lungs after maximal inspiration (thesum of all volume compartments)

• Change in lung volumes and capacities in various disease states

Dynamic property – It is resistance offered by the airways to air flowDepends on the net diameter of the airwaysDuring quiet mouth breathing, the mouth, pharynx, larynx, and trachea constitute 20 to 30 percent of the airway resistance;

Most of the remainder of airway resistance is in medium sizedlobar, segmental, and subsegmental bronchi

the small peripheral airways, particularly those less than2 mm in diameter, constitute only about 10 to 20 percent ofthe total airway resistance. because the net total diameter of them is very large compared to proximal airways

Airway resistance varies with inspiratory and expiratory phases of respiration because of presence of collapsible walls in airways

resistance is less during inspiration compared to expiration due to pull by surrounding parenchyma during its expansion caused by more negative intrapleural pressure during inspiration.so air way disease like asthma affects the airflow rate more during expiration

Air way resistance is also inversely proportional to lung volumes

Pulmonary function tests(PFT)

it includes following objective methods to asses the lung function

SpirometryBlood gasesLung volumes by helium dilution or body

plethismographyDiffusion capacity Bronchial challenge test

Spirometry measures the pattern of air movement into and out

of lungs during controlled ventilatory maneuvers

Expiratory flow ratesForced vital capacity(FVC) total volume of air that can be exhaled from TLC forced expiratory volume in 1st second(FEV1)- 75%-80% of FVC

Grading of obstruction basing on FEV1/FVC% >75% normal60%-75% mild obstruction50%-59% moderate obstruction<49% sever obstruction

Forced mid expiratory flow rate-FEF (25%-75%) • It is flow rate between 25% and 75% of FVC

indicated by slope of FVC volume time curve. expresed as lit/sec

• It corresponds to smaller airway dynamics

Interpretation of FEF(25%-75%) with respect to % of predicted value

>60% normal 40%-60% mild obstruction 20%-40% moderate obstruction <10% sever obstruction

Forced mid inspiratory flow-FIF(25%-75%)• It is calculated similar to FEF(25%-75%).• It is dependent on the respiratory effort and

function of respiratory muscles a drop in mid inspiratory flow is more sensitive

indicator of respiratory muslce dysfunction or suboptimal effort

Forced inspiratory volume-time curve.

Flow volume relationships it is studying the variation in air flow with change in

lung volume

Expiratory flow volume curves

Inspiratory flow volume curveDuring inspiration the diameter of the airway remains

same throughout the inspiration(due to stretch by surrounding expanding parenchyma) and the flow predominantly depends on pressure gradient across the airway. this results in grossly symmetrical curve

Normal Flow volume loop

Fixed central air way obstruction eg trachial scarring after tracheotomy in this the obstruction remains same through

out respiratory cycles so both expiratory and inspiratory flows are equally affected

volume

Variable obstruction in this the degree of obstruction varies in different

phases of respiration the phase of respiratory cycle affected

depends upon the location of obstruction in tracheobronchial tree

variable extrathoracic(tracheomalacia) – inspiratory phase is affected

During expiration tracheal pressure is more than atmospheric pressure so it remains open during expiration resulting in normal expiratory flow

airfl

ow

variable intrathoracic obstuction obstruction is less during inspiratory phase as

airways remains patent during inspiratory phase due to pull by surrounding parenchyma

volume

airfl

ow

• Flow volume loop in obstructive diseases airway obstructive diseases-asthma/COPD both

expiratory and inspiratory flows are affected with relative preservation of expiratory flow pattern

volume

airfl

ow

• Flow volume loops in restrictive lung diseasesIn this the normal configuration of both expiratory

and inspiratory limbs are preserved but the peak flow and volumes are reduced

Diffusion capacity it is a measure of amount of gas exchanged across

the alveolocapillary membrane(interstitium)

CO gas is used because itdoes not reach equilibrium b/w alveoli and pulmonary capillary blood in a cardiac cycle duration(0.75sec), as it has high affinity to hemoglobin that prevents the Pco in capillaries to raise ,i.e CO exchange is diffusion-limited

Diffusion capacity of CO (DLco) it is dependent on the surface area available for diffusion thickness of interstitium haemoglobin in capillariesNormal DLco at rest is 25ml/min/mm hg it is decreased in pulmonary fibrosis(ILDs)-increas intertial thickness emphysema-decreases surface area pulmonary hypertension-decreases pulmonary flow anemia

FEV1/VC≥ LLN

VC ≥ LLN VC ≥ LLN

TLC ≥ LLNTLC ≥ LLN

Obstruction Mixeddefect

DL,co ≥ LLN DL,co ≥ LLN

DL,co ≥ LLN

NormalPVdisorders

CW and NMdisorders

ILDPneumonitis

AsthmaCB

Emphysema

yes

yes

yes

no

no

restriction

no

no

no

no

yesyes

no no

yesyes

Breath-Holding test of Sebrasez

Match Blowing Test

Valsalva Test

Single Breath Count

Ascultation over Trachea

Cough test

Bed side pulmonary function tests

Interstitial lung diseases (ILDs)

ILDS are defined as- collection of non neoplastic lung disorders both acute

and chronic ,that are not caused by known infectious agents presenting with variable degrees of inflammation and fibrosis-fishman

ILDs are also termed as diffuse parenchymal lung diseases(DPLD)

They predominantly involve interstitium of the lung (alveolar epithelium , pulmonary capillaries with its endothelium , stroma in between them along with lymphatics) but airways may also get involved occasionally

>200 known individual diseases involving pulmonary interstitium are present, these diseases can be classified together because of clinical , pathological and radiological similarities

When to suspect ILDs in all patients who present with constitutional symptoms of fever ,weight loss ,

asthenia and respiratory symptoms of cough ,dyspnea ,chest pain should be evaluated for known infectious/other hypersensitive respiratory disorders

when the features of respiratory involvement are progressive /relapsing and remitting type that do not respond to usual management than ILDs are suspected only after evaluating for other treatable causes

classification of ILDs

In to two major groups based on underlying histopathology

interstital FIBROSIS/ GRANULOMAEach major group into subgroups based on

etiological factor KNOWN cause/UNKNOWN cause

ILDsIntertial fibrosis

Known causeunknown cause

1.asbestos

2.fumes,gases3.drugs

4.radiation

5.smoking

a.Desquamative interstitial pneumoniab.respiratory bronchiolitis associated ildc.Langerhans cell granulomatosis

Granulomas in interstitium/vasculature

Intertial fibrosis with unknown cause1.Ideopathic interstitial pneumonia

a.Idiopathic pulmonary fibrosis UIP

b.Acute interstitial pneumonia AIPc.Cryptogenic organizing pneumonia BOOP

d.Non specific interstitial pneumonias

2.ILDs associated with connective tissue disordersSLE, RA, ankylosing spondylitis systemicsclerosis ,sjogrens ,polymyositis ,dermatomyositis

3.Pulmonaryhemorrhage syndromesGoodpastures,ideopathic pulmonary hemosiderosis, isolatedpulmonary capillaritis

4.Inherited diseasesTuberous sclerosis,NF,niemann pick,hermansky pudlak

5.gastointestinal/liver diseasesCrons,ulcerative colitis,primary biiar cirrosis,chronic active hepatitis6.Pulmonary alveolar proteinosis7.Eosinophilic pneumonias8.Lymphangio leomyomatosis9.amyloidosis

Granulomas in interstitium/vasculature

Known cause

unknown cause1.Hypersensitivity pnemonitis

Organic dusts Inorganic dustsBeryllium,silica

1.sarcoidosis

2.Granulomatous vasculitidisa.wegnersb.churg-straussc.Benign lymphocytic angitis

d.Necrotising sarcoid granulomatosis

3.Lymphomatoid granulomatosis4.Bronchocentric granulomatosis

Pathogenesis following initial injury to airway/alveoli either due

due to autoimmune cause/known antigen-organic or inorgnaic surce ,drugs ,toxins in tobbaco

inflamatory cell infiltration ,exudatioin ,cytokine release causing metabolic and other functional abnormalities in alveolar interstitial components

If the insult continues to persist leading to chronicity

Lymphocyte infiltration progressive depositionEpitheloid cell formation of collagen leading to Surrounding areas of focal interstitial fibrosis

fibrosis and honeycombing

(GRANULOMA) formation

Most common ILDs 1. ideopathic interstitial pneumonias 40% a.ideopathic pulmonary fibrosis 55% 2.occupational and environmental 26 % Least common ILDs pulmonary haemorrhage syndromes <1%

Retrospective study of interstitial lung disease in a tertiary care centre in India.indian journal of chest diseases and allied sciences

Idiopathic pulmonary fibrosis (43%), sarcoidosis (22%), ILDs secondary to collagen vascular disease (19%)

and extrinsic allergic alveolitis, among others, were the

most common aetiological causes of ILD.

Clinical presentation

symptoms dyspnea cough-dry hemoptysis-ILDs associated with CTD pulmonary hemorrhagic syndromes chest pain/pleurisy fever weight loss Features of CTD- skin rash, raynauds phenomenon,

. arthritis , proximal muscle weakness sinusitis-wegeners granulomatosis

age at presentation most of ILDS present at 20-40 yrs 1.ILDs associated with connective tisssue disorders 2.ILDs with inherited causes- familial IPF gauchers hermansky-pudlak 3.lymphangioleiomyomatosis 4.langerhans cell granulomatosis

ILDs that manifest during infancy and childhood 1.follicular bronchitis 2.cellular interstitial pneumonia 3.acute idiopathic pulmonary hemorrhage of

infancy idiopathic pulmonary fibrosis (IPF) manifests after 60 yrs

Duration of symptomsAcute onset: days to weeks• Acute interstitial pneumonia• Acute pneumonitis from collagen vascular disease(especially SLE)• Cryptogenic organizing pneumonia• Drugs• Diffuse alveolar hemorrhage• Eosinophilic lung disease• Hypersensitivity pneumonitis

Subacute: weeks to months• Collagen vascular disease–associated ILD• Cryptogenic organizing pneumonia• Drugs• Subacute hypersensitivity pneumonitis

Chronic: months to years• Chronic hypersensitivity pneumonitis• Collagen vascular disease–associated ILD• Idiopathic pulmonary fibrosis• Nonspecific interstitial pneumonia• Occupation-related lung disease (e.g., silicosis,• asbestosis)

Gender variationCommon in females 1.ILDs associated with connictive tissue diseases

except in RA 2.lymphangioleomyomatosis 3.ILDs in tuberous sclerosis,hermansky pudlackCommon in males 1. ideopathic pulmonary fibrosis 2.pneumoconiosis

exposure history Hypersensitivity pneumonitis • Bird breeders• Farmers• Bark strippers/wood workersInorganic dustAsbestosis• Automotive mechanics , Electrician , Pipefitters ,

Shipyard workersberylliosis• Electronic and computer,industry workersCoal workers pneumoconiosissilicosis

Certain ILDs are also associated with smoking and drug intake so possibility of such association should be considered in history

In a patient with ILDS Family history of connective tissue disorders , sarcoidosis ,tuberous sclerosis should also be enquired

Signs on examination usually these are non specific tachypnea cyanosis clubbing velcro rales inspiratory squeaks- cryptogenic organising pneumo constrictive bronchiolitis hypersensitivity pneumonitis exta pulmonary signs in systemic diseases with lung involvement

Investigations 1.hematologicl/serological they provide supportive evidence CBC- eosionphilia , LFT , RFT, serum calcium , serum ACE, complement levels serum autoantibody- ANA ,anti dsDNA ,anti sm RF ,anti Jo ,p/c ANCA

radiological investigations Xray is basic – usually the findings are nonspecific it

may show reticular/nodular/mixed opacitis with varied distribution depending upon the disease

HRCT is gold standard for imaging as it reveals characteristic findings that are highly suggestive of diagnosis

Pulmonary function tests spirometry- most of the ILDs produce restrictive

pattern with - reduced TLC , FVC ,FRC ,RV normal/increased FEV1/FVC restrictive+obstructive pattern seen in lymphangioleomyomatosis sarcoidosis langerhans cell histiocytosis constirctive bronchiolits hypersensitivity pneumonia Spirometric values are proved to have prognostic

value in IPF, non specific interstitial pneumonia

Diffusion capacity most ILDs have reduction in CO diffusion.it is

attributed to- V/Q mismatch effacement of alveolar capillary unitsThe severity in reduction of diffusion capacity of lungs

does not correlate with disease stageCardio pulmonary exercise testing(6 minute walk test) these tests are used to identify the subtle

abnormalities in gas exchange in ILD patients who have normal gas exchange at rest

Bronchoalveolar lavage(BAL) it is of diagnostic importance in 1.sarcoidosis - lymphocytosis, CD4/CD8 >3.5 2.pulmonary alveolar proteinosis- Milky BAL fluid

with debris and foamy macrophages3.eosinophilic pneumonias-eosinophils >25%4.Pulmonar langerhans cell histiocytosis- CD1+

langerhans cells,birbeck granules in macrophages5.berylliosis- positive lymphocyte transformation test

to beryllium6.asbestosis-dust particles ferruginous bodies

tissue biopsyIt is the most effective method of confirming the

diagnosis and acessing the disease activityMultiple transbronchial biopsies are more sensitive in

sarcoidosis , hypersensitive pneumonitis , organising pneumonia ,respiratory bronchiolitis associated ILDs.

if transbronchial biopsy does not suggest specific diagnosis lung biopsy by thoracoscopy or thoracotomy is necessary

Lung biopsy is contraindicated in end stage of disease,elderly ,cardiovascular compromise

Idiopathic pulmonary fibrosis(IPF)It is a specific form of fibrosis confined to lung with

characteristic radiological and histological appearance

Risk factors- age family history of IPF smoking clinical features Age >50 y chronic symptoms-dyspnea,cough Velcro rales, clubbingHRCT: Peripheral, subpleural,basal Reticular opacities. Honeycombing. Traction bronchiectasis

Idiopathic pulmonary fibrosis. This high resolutioncomputed tomogram of the chest demonstrates classic bilateralhoneycombing.

Bilateral, peripheral, and subpleural honeycomb changes (arrowhead) and traction bronchiectasis (arrow).

Histology- a. patchy interstitial infalmmation with lymphoplasmacytic infiltration. b. cystic fibrotic air spaces lined by

bronchiolar epithelium and filled with mucin

honeycomb change (arrowheads) present in the regionof dense fibrosis adjacent to the pleural surface. A fibroblast focus(arrow) is seen at the leading edge of advancing fibrosis.

Major criteria• Exclusion of other known causes of ILD, such as certaindrug toxicities, environmental exposures, and connective

tissue diseases• Abnormal pulmonary function studies that include

evidence of restriction (reduced VC often with an increased FEV1/FVC ratio) and impaired gas exchange [increased AaPO2 with rest or exercise or decreased DlCO]

• Bibasilar reticular abnormalities with minimalground glass opacities on HRCT scans

• Transbronchial lung biopsy or bronchoalveolar lavage (BAL) showing no features to support an alternative diagnosis

Minor criteria• Age greater than 50 years• Insidious onset of otherwise unexplained dyspnea

on exertion• Duration of illness greater than or equal to 3

months• Bibasilar, inspiratory crackles (dry or “Velcro” type

in quality) IPF is considered “likely” if the patient is an immunocompetent adult and all 4 major criteria

+ 3 minor criteria

TreatmentIt is not indicated for all IPF PatientsPatients whose clinical features suggestive of more

favourable outcome will have more benefit from therapy

Oxygen supplement for patients with hypoxemia at rest SPo2 <88%

Drugs –immunosuppressant's-

corticosteroids ,azathioprine ,cyclophosphamide ,interferon γ1b

Antioxidants-N acetyl cysteine

Criteria for lung transplantation• Pathologic or radiographic evidence of IPF and any of the following criteria

• DLCO <39%• Decrement in FVC 10% during 6 months of follow-

up• Decrease in SpO2 below 88% during a 6-min walk

test• Honeycombing on HRCT

• Secondary causes of IPF-pneumoconiosis ,radiation injury ,chronic aspiration ,organized chronic eosinophilic pneumonia

Nonspecific interstitial pneumonia It is a subacute process affects young women, non smokers HRCT Peripheral, subpleural,basal, symmetric Ground-

glass,opacities with Lower lobe volume loss. honey combing is rare

Peripheral ground glass opacities with tractional bronchiectasis

Histology

Treatment Immunosuppressents –glucocorticoids, azathioprine

uniform interstitial involvement with cellular infiltration or fibrosing pattern little or no honeycombing is found.

majority of patients with NSIP have a good prognosis (5-year mortality rate estimated at <15%

There is a lymphoplasmacytic infiltration of the interstitium

Acute interstitial pneumonia(hamman rich syndrome)

considered as idiopathic cause of ARDSpresents asAbrupt on set of fever ,cough ,dyspnea after a

prodromal illness

HRCT b/l symmetrical patchy ground glass opacities in subpleural distribution

Histology leucocyte infiltration interstitial edema which

in later stages shows interstitial fibrosis

Diagnosis of AIP requires in clinical presentation like ARDS and pathological conformation of diffuse organising alveolar damage

Treatment as most have hypoxemia with respiratory failure

mechanical ventilation with supportive care is required. Benefit of glucocorticoid usage is unknown

Mortality rate is about >60% in first 6 months

cryptogenic organising pneumonia(COP)Clinical features presents during 40-50 yrs, common in non

smokers .has subacute course of fever, cough and other constitutional features with inspiratory crackles on examination

HRCT Reverse halo sign/attol sign it is central area ground glass opacity (distal air

way infiltration)surrounded by a more dense crescent or ring shaped shadow(granulation tissue in wall of air ways

Histology collagen deposition and narrowing of alveolar ducts.

formation of granulation tissue polyps(masson bodies)consisting of macrophages and fibrous tissue in small airways alveolar ducts,air spaces

Masson body

Treatment immunosupressents like glucocoricoidsIt induces remession in about 2/3rds but rest may

progress despite the therapy

Pulmonary langerhans cell histiocytosis(PLCH) langerhans cell is a reticuloendothelial cell derived

from macrophagePLCH is characterised by langerhans cell infiltration Etiological factor-smokingIt is also associated with malignancies like NHL,HL Presentation –young male (20ysr-40 yrs) chronic smoker nonproductive cough ,dyspnea ,weight

loss ,chest pain

Xray –illdefined nodular(2-10mm) ,reticular opacities with cysts in middle to upper zones and sparing of costphrenic angles

ill-defined nodules, reticulonodular opacities,cysts, costophrenic angle sparing, and preservation of lung volumes.

HRCT-combination of thin walled cysts with nodules

PFT-decreased DLco with restrictive/obsrtuctive patterns

Tissue biopsy poorly defined bronchiolocentric nodular sclerosing

lesions containing clusters of langerhans cells .langerhans cells show birbeck granules

central bronchiole ( ) is dilated, and adjacent ∗alveolar spaces have coalesced because of focal destruction of alveolar walls

Electron micrograph of Langerhans’ cell (Lg) of the lung. Typical X bodies (Birbeck granules)

ComplicationsPneumothraxHemoptysisPulmonary hypertension Treatment Stopping of smoking Corticosteroid therapy is less usefulAnti TNF α has evidence of improvement

Lymphocytic interstitial pneumonitis(LIP)Common in adult(>50yrs) femalesusually associated with CTDPresents with nonspecific respiratory featuresAbout 20% has salivary gland enlargementXRAY-b/l lower zone reticular opacitiesHRCT –lower lobe ground glass opacities with

centilobular/subpleural pulmonary nodules

Ground glass changes with pulmonary nodules

HistologyCharacterised by lymphocytic infiltration , germinal Center formation

within the interstitium

Treatment Corticosteroidsabout 30% can progress to end stage fibrosis

Pulmonary lymphangioleiomyomatosis affects young women, common in whitesCharacterised by atypical proliferation of pulmonary

inerstitial smooth muscle and cyst formationClinical features dyspnea ,cough ,chest pain accelarated during pregnency, abates after

oophorectomyIt should be suspected in young woumen with

emphysemaComplications-

hemoptysis ,pneumothorax ,chylothorax

PFT- obstructive/ mixed pattern

multiple thin-walled cystic airspaces.Surrounded by normal lung Pulmonary lymphangioleiomyomatosis causes

thin-walled emphysematous spaces leading to the distinctive type of honeycombing.

There is no proven beneficial therapyProgesteron and luteinizing hormone analogues are

triedLung transplant is final consideration

Sarcoidosis a multisystem disease characterised by formation of

noncaseating granulomas Prevalence 20-60 per 1lakh population Common in females >40yrs,HLA DRB1*1101 smoking is associated with decreased riskClinical manifestations • Pulmonary (>90%) dyspnea,cough• Upper respiratory tract and oral cavity(5–10%)Hoarseness, laryngeal or tracheal obstruction, nasal

congestion, sinusitis

• Ocular (20–30%) - uveitis,retinitis, conjunctivitis, optic neuritis

• Skin (20–30%)- Erythema nodosum, lupus pernio, alopecia

• Hematologic (20–30%)- lymphadenopathy , splenomegaly , hypersplenism, anemia , lymphopenia

• Endocrine (10–30%)- Hypercalciuria, hypercalcemia, hypopituitarism, diabetes insipidus

• Neurologic (5–10%) -Facial and other cranial neuropathies, aseptic meningitis, seizures, obstructing hydrocephalus, myelopathy, polyneuropathy

• Cardiac (5–10%)- Arrhythmias, heart block, cardiomyopathy, sudden death

• Exocrine gland (10–20%)- lacrimal, and parotid gland enlargement, sicca syndrome

Liver,joints,muscles,renal and genitourinary systems are also involved

Investigations

Hematological –hypercalcemia ,raised ESR,hyper globulenima

Raised ACE levels in 60%-80%and is non specific

Kveim test-part of spleen of sarcoid patient injected intradermally and observed for granuloma formation after 4-6weeks

PFT restrictive pattern common than obstructive decreased diffusion capacity of CO

Radiological –Xray,HRCT staging

stage 1 hilar lymphadenopathy assosiated with right paratracheal adenopathy

stage 2 hilar lymphadenopathy+ pulmonar infiltrates

stage 3 pulmonry infiltrates alone

stage 4 fibrocystic changes

• BAL findings CD4/CD8 >3.5 to 4 supports a diagnosisTissue biopsy biopsy from easiest accessible site is used to confirm

a diagnosis of Biopsy of a skin or conjunctival nodule, enlarged

superficial lymphnode, or lacrimal gland will be sufficient if clinically involved if these sites are not involved trans bronchial biopsy(TBB) is needed

lungbiopsy showing extensive parenchymal involvement with granulomas, multinucleated giant cells, and mononuclearcell inflammation

Granuloma in lymphnode

Asteroid bodies

Diagnosis of sarcoidosis requires presence of clinical/radiological features suggestive of sarcoidosis with tissue biopsy showing noncasiating granulomas

Treatment Immunosuppressents - steroids azathioprine ,methotrexate hydroxychloroquin infliximab

EOSINOPHILIC PNEUMONIAIt includes disorders with eosinophilic pulmonary

infiltration with peripheral blood eosinophiliaIt is considered to be immunologically mediated with

varied precipitating eventsKnown causes unknown causesAllergic bronchopulmonary loefflers mycosisParasitic acute eosinophilic pneDrugs chronic eosinophilic pneEosinophilia myalgia syn hypereosinophilic syndr

Allergic bronchopulmonary mycosisIt is due to hypersensitive reaction to antigen of

inhaled fungi

Aspergillus fumigatus(mc)-ABPAPencillumCandidacurvularia ABPAIt usually presents as recurrent episodes of

cough,thick brown mucous ,dyspnoea ,wheez in a known asthmatic

• Diagnostic criteria of ABPA

Major

AsthmaPositive immediate hypersensitivity skin-prick test to AspergillusPrecipitating antibodies against AspergillusElevated total IgEElevated serum Aspergillus–specific IgE, IgGHistory of pulmonary infiltratesPeripheral blood eosinophilia+/− Proximal bronchiectasis

MinorMucous plugs containing AspergillusDual cutaneous reaction to Aspergillus

The imaging findings in ABPA• Tansient migratory pulmonary infiltrates usually in

upperlobes • Central bronchectas with mucoid impaction in

dilated bronchi appear as glove in finger opacity

ABPA. Extensive infiltrates withtubular configuration and ‘‘gloved finger” appearance are present, predominantly in the lower lobes

. Central bronchiectasisa patient with ABPA

• Basing on clinical ,radiological ,serological characters 5 clinical stages are recognised

Stage I: AcuteAcute asthma symptomsElevated serum IgE (>1000 IU/ml)Peripheral blood eosinophilia (may be absent in patients treated with oral coricosteroids)Fleeting infiltrates on chest x-ray (may be absent in patients treated with oral coricosteroids)Positive specific IgE, IgG, skin test reactivity, and precipitins to A. fumigatusResponds to steroids/antifungal therapy

Stage II: RemissionResolution of symptomsResolution of pulmonary infiltratesImprovement in eosinophilia and A. fumigatus specificblood abnormalities

Stage III: Exacerbation/recurrenceRecurrence/worsening of clinical symptomsRecurrent pulmonary infiltratesRising IgE levels

Stage IV: Steroid-dependent-asthmaRefractory steriod-dependent asthmaPersistently elevated serum IgE levelsPersistently elevated A. fumigatus–specific bloodabnormalities

Stage V: Fibrotic lung diseaseRefractory steriod-dependent asthmaFibrotic lung disease (irreversible obstructive andrestrictive defects with impaired diffusing capacity)Chronic bronchiectasis symptoms (sputumproduction, frequent infections)

Treatment of ABPAAcute stage- systemic glucocorticoid will reduce the

severity of symptoms duration of maintainence therapy is according to

stage early initation of therapy proved to reduce

progression to fibrosis

• Tropical pulmonary eosinophila this is due to hypersensitivity to antigens ofparasites

as Ascaris ,ankylostoma ,strongyloides ,toxocara ,Usually manifests as cough ,dyspnea , wheezing hyper infection syndrome results due to sever

autoinfection of parasites usually in immuno compromised patients presentation may be as ARDS

TREATMENT antihelminthic supportive measures

Drug induced eosinophilic pneumonia nitro furantoin penicillin sulfonamides isoniazid thiazides Tricyclic anti depressants indomethacin

hypersensitivity pneumonitis an ILD caused due to repeated inhalation of organic

agents by a susceptible host

A large number of agents are associated,presently common are

farmer’s lung disease, bird fancier’s disease, ventilator lung, Japanese summer-type HP

Disease Source AntigenFarmer’s lung disease Moldy hay

Thermophilic actinomycetesT. vulgarisAspergillus spp.

Bagassosis Moldy pressed sugarcane (bagasse

Thermophilic actinomycetesT. sacchariT. vulgaris

Bird fancier’s lung Domestic and wild bird products

Bird proteins

Ventilator lung

Contaminated humidifiers,dehumidifiers, air conditioners,heating systemsThermophilic

Thermophilic actinomycetes, T. candidus,T. vulgaris, Penicillium spp.,Cephalosporium spp.Amoebae Klebsiella spp.Candida spp.Basement lung Contaminated basement (sewage ormold)Cephalosporium spp.

Disease Source Antigen

Japanese summer house HP House dust, bird droppings(?)

Trichosporon cutaneum

Wood dust HP Contaminated wood dustBacillus subtilisAlternaria

Greenhouse lung Greenhouse soilAspergillus spp., Penicillium spp.,Cryptostroma corticale

Shell lung Oyster or mollusk shell Shell proteins

Basement lung Contaminated basement (sewage ormold)

Cephalosporium spp.Penicillium spp.

Pathophysiology susceptible host on repeated and prolonged

exposure to an antigen gets sensitised resulting in hypersensitivity reaction usually type 4 involving lung and formation of granulomas

Clinical features acute/subacute form – 6-8 hrs after exposure to

antigen cough , dyspnoea ,malaise ,fever with fine crackles

these features disappear in days to months if further exposure is avoided in few it can progress to chronic form with gradual worsening of cough ,dyspnoea

Investigations Raised ESR, CRP ,serum precipitins to suspected

antigenX RAY acute/subacute form –poorly defined/discrete

patchy/diffuse nodular infiltrates usually apical sparing

bilateral lower lobe 2- to 3-mmnodules.

Chronic stage-diffuse reticulonodular infiltrates with eventual honycombing

• HRCT ground-glass densities and diffusely increased pulmonary radiodensities.

patient with exposure to both birds and shells . Note the diffuse nodular lesions in the lower lobes, with areas of groundglassdensities posteriorly.

• PFT restrictive or obstructive or mixed pattern decreased diffusion capacityBAL – increased lymphocytic countLung biopsy in active stage- inflammatory cell infiltration with

granulomas in interstitium

lung biopsy from a patient with bird fancier’s disease.There is nonspecific interstitial mononuclear inflammation and loosely formed granulomatous lesions.

• Chronic stage –non specific interstitial and peribronchiolar fibrosis with or without granulomas

Treatment environmental control to reduce antigen exposure , glucocorticoids and supportive measures

• ILD associated with occupational inorganic dust exposure

AsbestosisAsbestos is a fibrous hydrated magnesium silicate

with more than 3000 commercial usesIt has 2 forms serpentine(chrysolite) commonly used

. amphibole less usedExposure occurs in cement industry,asbestos mining

Asbestosis refers to interstitial diseaseOther pulmonar manifestations arePleural plaque ,Benign pleural effusionMesotheliomasBronchogenic carcinoma

Asbestosis usally results after 20-30 yrs of exposureAnd presents as progressive cough and dyspnoea

XRAY in asbestosis b/l diffuse lowerlobe reticulonodular opacitie

bilateral calcified pleural plaques on top of the diaphragm. costophrenic angles are blunted. Mediastinalpleural calcification is present on the right.

• BAL –ferruginous bodies asbestos fiber surrounded by iron rich material

TreatmentStopping further exposure,avoiding smoking and other supportive measures

Silicosis exposure in stone quarries, sand blasting ,quartz

industriesPresents with nonspecific symptoms of

cough ,dyspnoea ,fatigue usually after several years of exposure

Acute silicosis symptoms occurs in few weeks to months after heavy exposure to dust with high quartz content

Silicotuberculosis –high prevalence of TB in silicosis

• XRAY small rounded opacities in upper zones ,calcified hilar lymphnodes appear as egg shell calcification

Anthracosis coal workers pneumoconiosis occurs due to

tissue reaction to inhaled coal dust Presents as nonspecific symptoms of cough with expectorant containing black particlesDyspnoea ,wheeze due to bronchiolitisIn advanced stages progressive massive fibrosis can

occurCaplans syndrome rheumatoid arhtritis with

pneumoconiosis (antracosis,silicosis)

• XRAY small rounded nodules in upper zones in case of simple CWP

In later stages larger nodules that progress to PMF

Bilateral masses of progressive massivefibrosis are seen.

ILDs associated with connective tissue disorders

There is varied response to immunological damage of lung tissue in various CTDs

1.Diffuse alveolar damage(DAD)Seen in acute pneumonia in SLE Polymyositis/dermatomyositis

Interstitial involvement is a common respiratory manifestation of the collagen vascular disorders

Nonspecific interstitial pneumonitis (NSIP)

seen in patients with rheumatoid arthritis, polymyositis/dermatomyositis, mixed connective-tissue disease, and scleroderma.

•Lymphocytic interstitial pneumonitis

Seen in primary Sj¨ogren’s syndrome secondary Sj¨ogren’s syndrome, associated with rheumatoid arthritis.

Seen in –rheumatoid arthritis SLE systemic sclerosis

Idiopathic pulmonary fibrosis

Bronchiolitis obliterans organizing pneumonia(BOOP)

Seen in - rheumatoid arthritis polymyositis/dermatomyositis

Parenchymal nodules

Noninfectious inflammatory parenchymal nodules occur in rheumatoid arthritis Sj¨ogren’s syndrome.

In rheumatoid arthritis they are called as necrobiotic or rheumatoid nodules. Seen in both pleura and lung parenchyma identical in appearance to a subcutaneous rheumatoid nodule.

In the lung parenchyma, these nodules are located in the interlobular septa and in the subpleural parenchyma.

These nodules comprise of histocytes, giant cells, and other mononuclear cells surrounding an area of fibrinoid debris

Necrobiotic rheumatoid nodule. There is a central area of fibrinoid debris surrounded by palisading histiocytes.

ILDs with diffuse alveolar hemorrhageIt includes good pastures syndrome ,ideopathic

pulmonary hemosiderosis other auto immune diseases that involve pulmonary capillaries

it is characterised by intertitial infiltration of inflamatory cells with capillarities,fibrinoid necrosis of interstitium , bleed in alveoli

Presentation-acute onset of cough, dyspnea ,fever ,hypoxemia ,hemoptysis ,impared renal function

BAL-hemorrhagic fluid

Xray-non specific diffuse alveolar opacities

diffuse bilateral alveolar infiltrates representing massive alveolar hemorrhage.

Lung/renal biopsy with immunoflurosence –specific pattern of involvement

linear deposition-good pastures granular deposition –HSP

Treatment-methyl prednisolone/plasmapheresis

large numbers of red blood cells within alveolar spaces in a patient with alveolar hemorrhage due to Wegener’s granulomatosis

Pulmonary alveolar protenosis(PAP)It is not a true ILD as there is no lung inflamation and

the architecture is well preserved.as it resembles ILD so is discussed here

Surfactent it is produced by type 2 pneumocytesIt is a mixture of

dipalmitoylphosphatidylcholine ,other lipids and proteins

The surfactant proteins help to maintain the phospholipid layer

• Surfactant proteinsSP-A it has regulatory function SP-BSP-CSP-D maintains other proteins in lipidlayer PAPIt occurs due to defective clearance of surfactant by

alveolar macrophages

They are key proteins for surfactant action

3 causes of PAP>90% is acquired –antibody to GM-CSFCongenital -due to mutation in SPB proteinSecondary-llysinuric pretein intoleranceAcquired varient occurs at 30yrs-50yrsClinical features dyspnea cough occasionally with gelatinous expectoration fatigue ,weight loss

InvestigationsBlood/serum - polycythemia ,increasd SP-A ,SP-

B ,anti GM-CSF antibodyBAL -anti GM-CSF antibody

b/l central middle and lower zone opacities-batwing appearance

ground-glass opacification with interlobular thickening.

ILDs associated with Smoking 1.desquamative interstitial pneumonia 2.respiratory bronchiolitis associated pneumonia 3.langerhans cell granulomatosis/oesinophilic granuloma ILDs associated with drugs

ACE inhibetros - eosinophilic pneumonia

β blockers- pulmonary fibrosis acute hypersensitivity pneumonitis organising pneumonias eosinophilic/infiltrative pneumonias

Amiodarone- pulmonary fibrosis pulmonary nodules organising pneumonias oesinophilic pneumoniasBleomycin- pulmonary fibrosis pulmonary nodules organising pneumoniasCarbamazepine- organising pneumonia acute hypersensitivity pneumonitis diffuse alveolar damage alveoler hemorrhage

Other drugs-cyclophosphamide , phenyton , pencillamine , propyl thiouracil,

ReferencesFishman 4th editionGanong 24th editionHarrison 18nth edition

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