INTERSTITIAL LUNG DISEASE: A CLINICAL OVERVIEW AND GENERAL APPROACH

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INTERSTITIAL LUNG DISEASE A CLINICAL OVERVIEW
AND GENERAL APPROACH

• Tasaduk Khan. MD.FRCP(UK).FCCP(USA).
• Senior Consultant pulmonologist.
• Security forces hospital, Riyadh.

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Items

• Definition
• Epidemiology
• Classification
• Pathogenesis
• Diagnosis
• Treatment
• Final comments

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Items

• Definition
• Epidemiology
• Classification
• Pathogenesis
• Diagnosis
• Treatment
• Final comments

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• HAMMAN and RICH were the first to describe (in
  1935 and 1944) four patients who died of rapidly
  progressive lung disease characterized by diffuse
  interstitial pneumonia and fibrosis.
• Interstitium
• Refers to the microscopic anatomic space bounded
  by the basement membrane of epithelial and
  endothelial cells.
• Within this interstitial space, fibroblast like
  cells (mesenchymal and connective tissue cells)
  and extracellular matrix components (interstitial
  collagens, elastin, proteoglycans) are present

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Items

• Definition
• Epidemiology
• Classification
• Pathogenesis
• Diagnosis
• Treatment
• Final comments

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Epidemiology

• It is more frequent than previously recognized.
• Incidence ranges from 3 to 26 per 100.000 per
  year.
• The prevalence of preclinical and undiagnosed ILD
  in the community is 10 times that of clinically
  recognized.
• Among these, IPF is the most common, representing
  at least 30 of the incident cases.

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Items

• Definition
• Epidemiology
• Classification
• Pathogenesis
• Diagnosis
• Treatment
• Final comments

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Diffuse Parenchymal Lung Disease (DPLD)
Idiopathic interstitial pneumonias
DPLD of known cause, eg, drugs or association,
eg, collagen vascular disease
Granulomatous DPLD, eg, sarcoidosis
Other forms of DPLD, eg, LAM, HX, etc
Idiopathic pulmonary fibrosis
IIP other than idiopathic pulmonary fibrosis
Respiratory bronchiolitis interstitial lung
disease
Desquamative interstitial pneumonia
Cryptogenic organizing pneumonia
Acute interstitial pneumonia
Lymphocytic interstitial pneumonia
Nonspecific interstitial pneumonia (provisional)
ATS/ERS Consensus Statement. Am J Respir Crit
Care Med. 2002165277-304.
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Items

• Definition
• Epidemiology
• Classification
• Pathogenesis
• Diagnosis
• Treatment
• Final comments

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Four proposed mechanisms and potential variations
in lung responses to inhaled agents
Inhaled environmental agents (fumes, dust, smoke)
Delivery persistence
Genetic predisposition
Alveolar epithelial cell injury
Biochemical
Wound healing (inflammation, coagulation,
epithelial/endothelial repair)
Immunologic Fibrotic
Chronic airflow obstruction
Pulmonary fibrosis
Normal
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Recent Hypothesis

• Inflammatory hypothesis
• Epithelial Cell Apoptosis
• Angiogenesis
• Abnormal Matrix Turnover
• Th1 versus Th2 Cytokines
• Growth Factor Production
• Altered Fibroblast Phenotypes
• Myofibroblast Recruitment and Maintenance

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AGEGENETIC FACTORSENVIRONMENTAL FACTORSNATURE
OF INJURY
LUNG INJURY

• Etiologic agent
• Recurrent vs single
• Endothelial vs epithelial

Histopathologic Pattern
DIP
RB-ILD
LIP
COP
NSIP
AIP
UIP
Inflammation
Fibrosis
Thannickal VJ, et al. Annu Rev Med.
200455395-417.
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Items

• Definition
• Epidemiology
• Classification
• Pathogenesis
• Diagnosis
• Treatment
• Final comments

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Approach to the Diagnosis of ILD

• Clinical
• History
• Physical
• Laboratory
• PFTs

• Radiology
• Chest X-ray
• HRCT

• Pathology
• Surgical lung biopsy

Primary care physicians
Pulmonologists
Radiologists
Pathologists
Multidimensional and multidisciplinary
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Diagnosis

• History
• The patient's age, cigarette-smoking status and
  sex may provide useful clues.
• Thorough medical history that must include a
  review of environmental factors, occupations,
  exposures, medication, and drug usage and family
  medical history.

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Age

• Infancy and childhood
• Follicular bronchiolitis
• Cellular interstitial pneumonia
• Acute idiopathic pulmonary hemorrhage of infancy

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Age (cont.)

• Before age 40
• Familial idiopathic pulmonary fibrosis
• Metabolic storage disorders
• Hermansky pudalic syndrome
• Other inherited interstitial lung diseases
• Collagen vascular disease- associated ILD
• LAM
• Pulmonary Langerhanscell granulomatosis
• Sarcoidosis
• After age 50 IPF 1 in 500 people over the age of
  75 yrs.

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Race

• Sarcoidosis occurs 10-12 folds among blacks.

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Gender

• Gender clearly affects the way patients present
  with pulmonary fibrosis Men tend to present
  later in the disease, whereas women tend to
  present earlier.
• Women
• Collagen vascular disease- associated ILD
• LAM
• Tuberous sclerosis
• Men
• Pneumoconiosis
• IPF

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History (cont.)

• Smoking related ILD
• Desquamative interstitial pneumonia.
• RBILD.
• Pulmonary Langerhans cell histiocytosis.
• IPF.
• Rheumatoid arthritis associated ILD.
• Acute eosinophilic pneumonia.

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ILD by onset and duration

• Acute onset (days to weeks)
• AIP
• Acute pneumonitis from collagen vascular disease
  (especially SLE)
• COP
• Drugs
• DAH
• Eosinophilic lung disease
• Hypersensitivity pneumonitis

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ILD by onset and duration (cont.)

• Subacute (weeks to months)
• Collagen vascular disease- associated ILD
• COP
• Drugs
• Subacute hypersensitivity pneumonitis
• Chronic (months to years)
• Chronic hypersensitivity pneumonitis
• Collagen vascular diseaes- associated ILD
• IPF and NSIP
• Occupation related lung diseases.

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Physical examination

• Physical examination of the respiratory system is
  rarely helpful in the diagnostic evaluation of
  interstitial lung diseases.
• The classical Velcro rales or inspiratory
  crackles, occur not only in most patients with
  IPF but also in many other interstitial lung
  diseases.

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Clubbing

• Eighty percent of patients with clubbing have a
  respiratory disorder.
• Among patients with ILD clubbing is found in
  25-50 of patients with IPF and 50 of patients
  with DIP and 75 of patients with ILD from
  rheumatoid arthritis.

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Chest Radiographic pattern

• First review previous chest radiographs as this
  allows the clinician to ascertain the onset,
  progression, chronicity and stability of
  patient's disease.
• A rare patient with ILD will present with a
  normal chest radiograph.
• When radiographic abnormalities are noted, their
  distribution and appearance are useful in
  narrowing the differential diagnosis of ILD.

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Radiographic Clues (cont.)

• Mid/upper lung field disease sarcoidosis,
  silicosis, ankylosing spondylitis, histiocytosis
  X.
• Lower lung field predominance asbestosis,
  idiopathic pulmonary fibrosis, collagen vascular
  disease.
• Kerley B lines congestive heart failure,
  lymphangitic carcinoma, LAM.
• Pleural plaques/ thickening asbestosis.

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Radiographic Clues (cont.)

• Photographic negative of pulmonary edema Chronic
  eosinophilic pneumonia.
• Recurrent pneumothorax
• Langerhans cell granulomatosis.
• LAM
• Tuberous sclerosis.
• Neurofibromatosis.

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Computed tomography and high-resolution CT images

• CT and HRCT scans are more sensitive and have a
  greater ability to detect anatomic abnormalities
  than do chest radiograph.
• Its impressive sensitivity help both in ruling
  out a diagnosis of ILD and in defining the
  parenchymal, pleural and mediastinal
  abnormalities in these disorders.
• It helps the surgeon to identify areas of
  non-fibrotic, active disease and relatively
  unaffected areas to guide appropriate site
  selection for biopsy.

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Computed tomography and high-resolution CT images

• HRCT has the potential for differentiating
  sarcoidosis, lymphangitic carcinomatosis and
  bronchiolitis.
• The presence of cystic images within the
  parenchyma raises the possibilities of three
  major cystic ILD
• LAM, Tuberous sclerosis and Langerhans cell
  granulomatosis
• In LAM and Tuberous sclerosis, the cysts are
  numerous, thin walled, typically less than 2 mm
  in diameter and distributed throughout the
  pulmonary parenchyma.
• In Langerhans cell granulomatosis cysts are
  bizar shaped and distributed predominantly in the
  upper lobes.

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Computed tomography and high-resolution CT images

• In acute hypersensitivity pneumonitis HRCT show
  multifocal diffuse ground glass attenuation
  despite a normal chest radiograph.
• Smokers with symptomatic RBILD typically have
  patchy ground glass attenuation on HRCT.
• IPF is characterized by patchy subpleural and
  basilar fibrosis.
• A normal HRCT does not exclude the presence of
  microscopic ILD in a patient with a high pretest
  probability of the disorder.

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Pulmonary physiology testing

• Regardless of the cause, a restrictive lung
  defect and decreased diffusing capacity (DLco)
  are the predominant physiological abnormalities
  seen in ILD.
• Decreased FEV1, FVC, TLC
• The (PAO2 PaO2) difference, at rest or with
  exercise may be normal or increased.

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• Differential diagnosis by function
• When there is a decrease in MVV out of proportion
  to the decrease in FEV1 and a decrease in maximal
  inspiratory pressures, diseases such as
  polymyositis, scleroderma and SLE should come to
  mind.
• A mixed pattern of obstructive and restrictive
  abnormalities may be present when ILD coexists
  with COPD or Asthma.

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Routine laboratory tests

• Include
• Complete blood count, leucocytic differential
• ESR
• Chemistry profile (calcium, liver function tests,
  electrolytes, renal function tests)
• Screening for collagen vascular diseases and
  urine analysis.
• When appropriate, creatinine kinase, aldolase,
  and angiotensin converting enzyme levels should
  be measured.

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Bronchoscopy with transbronchial biopsy

• Provide additional information, especially when
  tissue abnormalities tend to be distributed in
  peribronchiovascular areas e.g. Sarcoidosis, LAM
  and Lymphangitic carcinomatosis.
• It may disclose certain distinctive abnormalities
  e.g.
• Tight, uniform, well formed non caseating
  granulomas of sarcoidosis.
• Smooth muscle proliferation of LAM.
• Lymphatic metastasis of malignant cells.
• Giant cell granulomas are suggestive of hard
  metal pneumoconiosis.
• It is diagnostic if an infectious agent or
  malignancy is detected.

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Surgical lung biopsy Thoracoscopy-Guided and
open lung biopsy

• Surgical lung biopsy remains the gold standard
  for diagnosis. It is, however, by no means always
  definitive the size of specimens, site of
  biopsy, expertise of pathologists and
  interobserver differences among pathologists are
  factors that may preclude a conclusive diagnosis.
• The site of the biopsy should be chosen on the
  basis of HRCT findings and ideally be at the
  interface of involved and less involved lung
  tissue.
• A biopsy of more than one site in the lung is
  more helpful.

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Diagnostic approach to suspected ILD
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American Journal of Respiratory Cell and
Molecular Biology VOL.29, 2003
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Items

• Definition
• Epidemiology
• Classification
• Pathogenesis
• Diagnosis
• Treatment
• Final comments

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Treatment

• The therapeutic regimen used for patients with
  ILD needs to be tailored to the patient and the
  disease process (disease-specific intervention).
• Avoidance of the offending agent or its
  environment.
• The use of corticosteroids, alone or in
  combination with immunosuppressives
  (azathioprine, cyclophosphamide) is currently
  recommended for most patients with chronic
  fibrotic lung disorders.
• However the clinical response is variable and
  unpredictable, some ILDs generally have a better
  prognosis and response more favorably than do
  others.

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Other measures

• Plasmapheresis is indicated in intractable and
  severe cases of alveolar hemorrhage syndrome
  resistant to corticosteroids and
  immunosuppressives.
• Supplemental oxygen is indicated to maintain
  adequate oxygen saturation.
• Unless contraindicated, all patients should
  receive pneumococcal and periodic influenza
  vaccinations.
• Other supportive measures such as rehabilitation
  are indicated in appropriate patients.
• Lung transplantation is a viable surgical option
  for selected patients who don't respond to
  currently available therapeutic regimens.

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Items

• Definition
• Epidemiology
• Classification
• Pathogenesis
• Diagnosis
• Treatment
• Final comments

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Final Comments

• The interstitial lung diseases are a fascinating
  collection of lung diseases that occur at any age
  group and may develop as a consequence of an
  extraordinarily broad collection of systemic
  diseases.
• The importance of a careful history and physical
  examination cannot be overstated, and may obviate
  many expensive diagnostic tests.
• The diagnosis and management of interstitial lung
  diseases often requires active discussion and
  collaboration between the clinician, surgeon,
  pathologist and radiologist.

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THANKS