European Respiratory Society
Interstitial Lung Diseases

Interstitial lung diseases represent an expanding field of respiratory medicine and pose important daily challenges for lung physicians. There have been tremendous advances in recent years in the understanding of the genetic basis and pathogenesis of a wide range of interstitial lung diseases. This book aims to highlight current challenges, open questions and international concerns, and to discuss a wide range of interstitial lung diseases in innovative contributions from experts from around the world.

  • European Respiratory Society Monographs
  1. Page vii
  2. Page viii
  3. Page ix
  4. Page 1
  5. Page 7
    Correspondence: M.K. Han, 3916 Taubman Center, 1500 E. Medical Center Drive, Ann Arbor, MI 48109-0360, USA. E-mail:

    Interstitial lung diseases (ILDs) are a heterogeneous group of parenchymal pulmonary disorders with varying histological appearances. The majority of ILDs share common restrictive physiological abnormality on pulmonary function testing. A growing body of literature suggests that exercise testing provides diagnostic and prognostic value in ILD.

    The 6-min walk test (6MWT) and cardiopulmonary exercise test (CPET) are two exercise tests that have been extensively studied in this patient population. While it has been demonstrated that there is good correlation between 6-min walk distance (6MWD) and peak oxygen uptake as measured by CPET in end-stage lung disease, the 6MWT should be considered complementary to the CPET as the 6MWD is probably more a reflection of functional exercise capacity for activities of daily living.

    From a diagnostic standpoint, exercise-induced hypoxia may be an early indicator of disease before the development of pulmonary function abnormalities. The CPET, in particular, demonstrates a distinctive pattern in ILD characterised by decreased tidal volume, increased respiratory frequency, reduced aerobic capacity and a widening of the alveolar–arterial oxygen tension difference during exercise. Cardiovascular abnormalities during exercise are also common in ILD patients. From a prognostic standpoint, desaturation during 6MWT, and 6MWD, are both predictive of mortality in idiopathic pulmonary fibrosis, as is hypoxaemia during CPET. The prognostic utility of the 6MWT and CPET in sarcoidosis is less clear but both may aid in the detection of early disease. In ILD associated with systemic sclerosis (SSc-ILD), the multisystem nature of the disease, including circulatory and neuromuscular abnormalities, leads to multifactorial exercise limitation such that the 6MWD is not reflective of the same physiological processes across individuals, which limits its prognostic value. Desaturation during CPET in SSc-ILD, however, does correlate with survival.

  6. Page 24
    Correspondence: K.R. Flaherty, Division of Pulmonary and Critical Care Medicine, University of Michigan, A. Alfred Taubman Health Care Center, 1500 E. Medical Center Drive Room 3916, Ann Arbor, MI 48109-0360, USA. E-mail:

    Assigning an accurate diagnosis for patients with idiopathic interstitial pneumonias (IIPs) is difficult but important as the prognoses and approach to treatment vary. Although clinical history and computed tomography are critical in the diagnostic process, they provide a confident diagnosis without a surgical lung biopsy in only a minority of cases.

    Knowledge and progress in disease classification, the understanding of disease pathogenesis and the development of novel therapies further emphasise the importance of achieving an accurate diagnosis.

    This chapter focuses on the rationale for obtaining a lung biopsy, describes which patients should undergo biopsy, highlights important risk factors, and describes how biopsy results are used in the overall management of patients with IIP.

    The final diagnosis requires the synthesis of clinical, radiological and histopathological information, often best accomplished in a dynamic, multidisciplinary approach. Diagnostic accuracy is essential as we strive to increase our ability to study and understand the biology, natural history and potential therapies for this group of devastating diseases.

  7. Page 36
    Correspondence: G. Raghu, Division of Pulmonary and Critical Care Medicine, Campus Box 356522, UW Medical Center, University of Washington, Seattle, WA 98195-6522, USA. E-mail:

    Fibreoptic bronchoscopy with bronchoalveolar lavage (BAL) is a minimally invasive and generally well tolerated procedure with very low morbidity and mortality. Importantly, the cells within the distal airways and alveolar surface provide potentially useful information regarding the pulmonary microenvironment involved with a disease process or in close proximity to it. This approach will continue to be helpful as more details of the normal lung are found and the pathogenesis of pulmonary diseases is explored.

    BAL has gained an important role in the evaluation of interstitial lung disease (ILD), which often represents a diagnostic dilemma. In a number of conditions, such as infections, malignancy and some rare ILDs, positive findings by BAL analysis – when present – may be sufficient to formulate a specific diagnosis, thus avoiding the need for more invasive procedures. In others, BAL may substantiate a variety of alternative specific diagnoses, provided appropriate laboratory studies are performed to identify the key features. Therefore, even when nondiagnostic, BAL cellular analysis usually provides valuable information in addition to the clinical and radiological data, and helps to narrow the differential diagnosis based on cellular patterns. Conversely, the diagnostic usefulness of BAL in idiopathic pulmonary fibrosis (IPF) – the most aggressive idiopathic interstitial pneumonia – is limited, and its most important application in the evaluation of patients with suspected IPF appears to be the exclusion of alternative diagnoses.

    While uniform and standardised techniques for collecting and analysing BAL fluid are needed, it is imperative that BAL cellular findings always be interpreted in the context of clinical and radiological data.

  8. Page 47
    Correspondence: T. Nukiwa, Dept of Respiratory Medicine (Respiratory Biology, Bioinformatics, and Medicine), Tohoku University Graduate School of Medicine, 1-1 Seiryo-machi, Aoba-ku, Sendai, 980-8574, Japan. E-mail:

    While the search for global and unbiased biomarkers for interstitial lung disease (ILD) using expression microarray analysis and proteomics is currently ongoing, ILD from any cause eventually results in type II pneumocyte injury and remodelling.

    The biomarkers KL-6/MUC1, surfactant protein (SP)-A and SP-D have been studied in Japan for more than 20 yrs and are currently in wide use. As characteristic type II pneumocyte-derived proteins, these biomarkers, are appropriate for disease evaluation in both serum and bronchoalveolar lavage fluid of patients with ILD, based on leakage from the alveolar space into the blood. KL-6/MUC1, SP-A and SP-D are produced mainly in type II pneumocytes, function in defence and modification of inflammation, and are upregulated in infection and injury of peripheral airspaces. Although these biomarkers show some variability in serum levels after injury due to large molecular size or multimer formation, they are useful as serum monitors in both acute and chronic ILD.

    In acute ILD, such as drug-induced pneumonitis, or hypersensitivity pneumonitis, or in acute lung injury of any origin, the levels of these biomarkers are high at onset, decrease following therapy, and eventually recover to within the normal range. In ILD with chronic and latent processes, including idiopathic interstitial pneumonias such as idiopathic pulmonary fibrosis, nonspecific interstitial pneumonia and cryptogenic organising pneumonia, as well as collagen vascular disease-associated interstitial pneumonia, these biomarker levels often are slightly high initially or in the early phase of computed tomography attenuation, and gradually increase as ILD progresses. Upon treatment, these biomarker levels usually decrease slowly, indicating a favourable response with regard to downregulation of lung inflammation, but not necessarily a relief of the patient's symptoms. Furthermore, these biomarkers can be used in combination with clinical parameters for survival prediction.

    Thus, type II pneumocyte-derived KL-6/MUC1, SP-A and SP-D are currently the best and most reliable biomarkers available for ILD management.

  9. Page 67
    Correspondence: J. Behr, Marchioninistr. 15, 81377 Munich, Germany. E-mail:

    Although there are interstitial lung diseases such as nonspecific interstitial pneumonia, which show favourable responses to anti-inflammatory therapy, the role of immunosuppressive therapy in idiopathic pulmonary fibrosis (IPF) is still unclear and well-designed, sufficiently powered studies to answer this question conclusively are lacking.

    The use of high-dose N-acetylcysteine as an antioxidant has shown promising results, but limitation of study design has generated some uncertainties regarding its efficiency and the necessity of combination with prednisone and azathioprine. These need clarification in a further trial, which has just been launched by the National Institutes of Health IPF-Net.

    Anti-fibrotic therapy for IPF has shown negative results for interferon-γ-1b in two large randomised controlled trials and negative primary end-points in phase 2 clinical trials for bosentan, etanercept and pirfenidone. Whereas subsequent studies of bosentan and etanercept are not yet available, pirfenidone has been studied in three additional phase 3 studies, of which two apparently showed positive results for the primary and several secondary end-points, but one did not. It would be premature to draw final conclusions, since the full paper publications of these studies are still pending.

    Taken together, we are left with many unanswered questions regarding the treatment of IPF and still there is no sufficiently effective drug therapy, since all studies could demonstrate stabilisation at best but no improvement. It appears that neither anti-inflammatory, nor anti-oxidative or anti-fibrotic therapy alone may provide a clue for the treatment of a complex disease like IPF, but combination therapy may be the future.

    The good news is that the past decade has represented a landmark phase for clinical trial development in IPF. It has clearly been demonstrated that multinational placebo-controlled trials can be performed in IPF and the landscape is bright with prospects for future trials.

  10. Page 87
    1. Page 87
      Correspondence: H.R. Collard, 505 Parnassus Avenue, Campus Box 0111, San Francisco, CA 94143, USA. E-mail:

      The idiopathic interstitial pneumonias (IIPs) are a heterogeneous group of diffuse lung diseases of unknown cause. Essential to an accurate diagnosis in patients with IIP is a multidisciplinary approach that integrates clinical, radiographic and pathological expertise.

      High-resolution computed tomography and surgical lung biopsy are important diagnostic tools, and complement the history and physical examination.

      Idiopathic pulmonary fibrosis (IPF) is the most common of the IIPs. It is crucial to separate IPF from other forms of IIP, since its therapeutic response and prognosis are particularly poor.

      The other IIPs include nonspecific interstitial pneumonia, cryptogenic organising pneumonia, acute interstitial pneumonia, respiratory bronchiolitis-associated interstitial lung disease, desquamative interstitial pneumonia and lymphocytic interstitial pneumonia.

    2. Page 112
      Correspondence: P. Cullinan, Occupational and Environmental Medicine, National Heart and Lung Institute, Imperial College, 1b Manresa Road, London SW3 6LR, UK. E-mail:

      For a comparatively rare disease, extrinsic allergic alveolitis (EAA) has attracted a remarkable number of wide-ranging reviews; we do not intend here to add to this but rather provide a focused discussion on some particular issues of contemporary concern.

      The first concerns phenotyping and the relative diagnostic values of clinical and investigative findings. Careful analysis of a multinational patient dataset suggests that a combination a just six factors provides, with high validity, a confident diagnosis. Cluster analysis of information from the same source indicates that the disease can be reduced to two phenotypes, usually referred to as “acute” and “chronic”, but perhaps better considered as “reversible” and “irreversible”.

      The second and third issues discussed relate to non-traditional causes of EAA, specifically domestic antigens (including those from feather bedding) and metal-working fluids (MWFs). The evidence for domestic aetiologies is entirely case based and involves a bewildering variety of antigens, almost always derived from moulds in damp housing. In contrast, there is increasing epidemiological evidence, in most cases from observed “outbreaks” of disease, that EAA arising from occupational exposure to MWF is under-recognised and often severe. Unfortunately, the causative antigen(s) remain(s) elusive but is likely to derive from microbial fluid contamination.

      Finally, we discuss the use of newer immunoglobulin G antibody assays, now almost universally offered in place of the traditional precipitating antibody test. While the newer tests are far simpler and quicker, and are probably easier to standardise, their diagnostic value, in particular their specificity and false-positive rate, remains very unclear.

    3. Page 126
      Correspondence: J.C. Grutters, St Antonius Hospital, Dept of Pulmonology, Center of Interstitial Lung Diseases, Koekoekslaan 1, 3435 CM Nieuwegein, The Netherlands. E-mail:

      Despite decades of research, sarcoidosis remains an enigmatic disorder in terms of aetiology, and also its pathogenesis is only partly understood. The prevailing hypothesis is that the disease is due to an altered or incomplete immune response to an auto- or alloantigen, such as (in-)organic particles of dust, a virus or a bacterium, that is inhaled into the lung of genetically susceptible hosts.

      Sarcoidosis is probably not a single disease, but a constellation of granulomatous diseases, each with its own triggering agent, a specific human leukocyte antigen (HLA) background, and a shared multitude of genes involved in granuloma formation and resolution. In particular, the acute form of sarcoidosis, i.e. Löfgren's syndrome, has a very strong association with HLA-DRB1*0301/DQB1*0201. In addition, the onset of this syndrome is associated with spring, giving rise to speculations concerning the trigging agent.

      To date, there is no single and specific test for the diagnosis sarcoidosis. It depends on the presence of compatible clinical, radiological and histological findings, and the exclusion of well-known causes of granuloma formation. Recent advances in the imaging of sarcoidosis include 18F-fluorodeoxyglucose positron emission tomography and magnetic resonance imaging, especially for the detection of cardiac involvement.

      Although there is still no curative treatment for sarcoidosis, there are several case reports, some case series, and a randomised, controlled trial showing promising results for the use of the tumour necrosis factor-α blocker infliximab, especially in cases of severe and/or refractory disease. However, further studies are needed to increase our knowledge on the optimal use of anti-tumour necrosis factor treatment in sarcoidosis.

    4. Page 155
      Correspondence: S. Harari, Unità Operativa di Pneumologia, Ospedale San Giuseppe, Via San Vittore 12, 20123 Milan, Italy. E-mail:

      Pulmonary Langerhans’ cell histiocytosis (PLCH), also known as histiocytosis X or Langerhans’ cell granulomatosis, is an uncommon granulomatous disease of unknown aetiology that represents <4% of all forms of interstitial lung disease.

      The disease occurs almost exclusively in young smokers. Langerhans’ cell infiltration is the pathological hallmark of PLCH. The presence of Birbeck's granules on electron microscopy and CD1a immunoreactivity make these cells unique. The disease is characterised by bronchiolocentric inflammation that forms stellate nodules with secondary vascular changes. The nodular lesions frequently cavitate and form thick- and thin-walled cysts, which are thought to represent enlarged airway lumina.

      The characteristic radiographic features of PLCH are bilateral nodular and reticulonodular areas of opacity that predominantly involve the upper and middle lung zones with relative sparing of the lung bases. High-resolution computed tomography shows nodules and cysts in the same distribution and allows a confident prospective diagnosis of PLCH in the appropriate clinical setting.

      In case of atypical presentation or radiological picture, the definitive diagnosis of PLCH requires lung biopsy. The course of the disease is variable, difficult to predict, and may range from spontaneous remission to progressive respiratory failure and death. Treatment consists of smoking cessation; corticosteroid therapy may be useful in selected patients. Chemotherapeutic agents and lung transplantation may be offered to patients with advanced disease.

    5. Page 176
      Correspondence: S.R. Johnson, Division of Therapeutics and Molecular Medicine, University of Nottingham, D Floor, South Block, Queen's Medical Centre, Nottingham NG7 2UH, UK. E-mail:

      Lymphangioleiomyomatosis (LAM) is a rare disease of the lungs and lymphatics occurring almost exclusively in females, generally developing before the menopause. It can occur sporadically or in association with tuberous sclerosis and is characterised by progressive pulmonary cystic change, recurrent pneumothoraces, chylous pleural collections and often progressive respiratory failure.

      Abdominal manifestations include lymphandenopathy, cystic lymphatic masses (lymphangioleiomyomas), chylous ascites and angiomyolipomas. Diagnosis is made by a combination of clinical features and computer tomography screening, or, in cases of doubt, lung biopsy. The only treatment for severe LAM at present is lung transplantation.

      As the number of patients diagnosed with LAM grows, our knowledge of the epidemiology and clinical features of the disease is changing. In addition developments in the cell biology and molecular pathways in LAM means that possible pharmacological therapies are being identified. Somatic mutations in the genes liked to tuberous sclerosis have been identified, and rapamycin may correct the resulting cellular abnormality.

      Here we review what is known about LAM, from bench to bedside.

    6. Page 208
      Correspondence: B.C. Trapnell, Room 4029, CCRF, Division of Pulmonary Biology, Cincinnati Children's Hospital Medical Center, 3333 Burnet Avenue, Cincinnati, OH 45229-3039, USA. E-mail:

      Pulmonary alveolar proteinosis (PAP) affects males, females, children and neonates and has a prevalence of 6–7 per million in the general population. It comprises a heterogeneous group of diseases that involve either reduced pulmonary clearance of surfactant or abnormal surfactant production.

      Diseases associated with reduced surfactant clearance include the common form, autoimmune PAP, which accounts for 90% of cases and is caused by a high level of granulocyte-macrophage colony-stimulating factor (GM-CSF) autoantibodies, and rare forms caused by mutations in one of the genes encoding GM-CSF receptor proteins (CSF2RA, CSF2RB). Secondary PAP accounts for 8–9% of cases and occurs in the context of another underlying disease, which presumably causes PAP by reducing either the numbers or functions of alveolar macrophages. Surfactant metabolic dysfunction disorders occur as a consequence of abnormal surfactant production caused by recessive mutations in genes encoding surfactant proteins (SFTPB, SFTPC), or a membrane lipid transporter critical to surfactant biogenesis (ABCA3).

      Reliable new methods are available for diagnosing clinical subtypes of PAP, in most cases without the need for a surgical lung biopsy. Notwithstanding, a high degree of clinical suspicion is required to avoid incorrect or delayed diagnosis, which occurs in many patients. Whole lung lavage remains the standard therapy for PAP caused by disruption of GM-CSF signalling, and is effective at physically washing surfactant from the lungs of most patients. Its role in secondary PAP is less clear and it appears to be of little utility in pulmonary surfactant metabolic dysfunction disorders.

      Novel pharmacological approaches, including inhaled or subcutaneous GM-CSF augmentation, or anti-CD20-mediated depletion of autoantibody producing B-cells are currently under evaluation of safety and efficacy as therapy of autoimmune PAP.

    7. Page 225
      Correspondence: A.L. Olson, National Jewish Health, 1400 Jackson Street, Denver, CO 80206, USA. E-mail:

      The connective tissue diseases (including rheumatoid arthritis, systemic lupus erythematosus, systemic sclerosis, Sjögren’s syndrome, polymyositis/dermatomyositis, and their associated overlap syndromes) are associated with a wide variety of pulmonary complications.

      While specific connective tissue diseases are typically associated with particular pulmonary complications, virtually all complications can occur with any of the connective tissue diseases and may even present prior to the diagnosis of the underlying connective tissue disease.

      Due to the resultant morbidity and mortality from these processes, pulmonary involvement needs to be recognized early, diagnosed accurately and treated aggressively. This requires all practitioners involved in the care of these patients to have a broad knowledge of these potential complications, including infection, drug toxicity, direct and indirect pulmonary complications of disease, and cardiovascular complications, for optimal care.

      Herein, we review these potential pulmonary complications and the impact of these complications within these specific connective tissue diseases.

    8. Page 251
      Correspondence: U. Specks, Mayo Clinic College of Medicine, Division of Pulmonary and Critical Care Medicine, Mayo Clinic, 200 First Street SW, Rochester, MN 55905, USA. E-mail:

      Pulmonary vasculitis is usually but one manifestation of a systemic autoimmune disease. The primary vasculitis syndromes that most commonly involve the respiratory tract are Wegener's granulomatosis (WG) and microscopic polyangiitis (MPA). They are small vessel vasculitides characterised by the presence of antineutrophil cytoplasmic autoantibodies.

      The clinical presentation of WG and MPA is determined by the type and location of predominant inflammation. Its severity influences the choice of remission induction therapy. Necrotising granulomatous inflammation most commonly affects the respiratory tract, is usually more slowly progressive, and is responsible for the disease manifestations of most patients categorised as having limited WG. In contrast, capillaritis leading to alveolar haemorrhage, glomerulonephritis or multiple mononeuropathies, is common to WG and MPA and results in severe disease.

      Glucocorticoids in combination with methotrexate (MTX) are the preferred treatment for patients with limited disease, whereas glucocorticoids in combination with cyclophosphamide (CYC), applied either orally on a daily basis or by intravenous bolus therapy, is required for patients with severe disease. In patients who rapidly progress to renal or respiratory failure, the addition of plasma exchange should be considered early. Once remission has been induced with CYC, this agent should be replaced by a remission maintenance agent after about 3–6 months of therapy.

      MTX or azathioprine are the best studied remission maintenance agents, and their efficacy and adverse events rate are equivalent. Mycophenolate mofetil can be used as a second-line agent for remission maintenance. Patients who are refractory to standard therapy or have contraindications to standard therapy are candidates for remission induction therapy with rituximab instead of CYC.

    9. Page 265
      Correspondence: C.S. Glazer, Division of Pulmonary and Critical Care Medicine, University of Texas Southwestern, 5323 Harry Hines Blvd, Dallas, TX 75390-8558, USA. E-mail:

      Occupational interstitial lung diseases (ILDs) are a diverse group of disorders of varied clinical presentation and pathogenesis. However, exposure in the workplace and home accounts for a significant portion of all ILDs and new exposures continue to be recognised as aetiological in ILD.

      Although some occupational ILDs have been recognised since antiquity, they continue to occur in the workplace and are often misdiagnosed as “idiopathic” when physicians miss the connection to past- or currently inhaled exposures. All of these diseases are preventable with reduction or elimination of workplace exposure. As a result, identification of occupational lung diseases is not only important for an individual's diagnosis, but also for prevention of disease in co-workers.

      This chapter reviews the spectrum of diseases caused by exposure to metal dust and fumes, inorganic fibres and nonfibrous inorganic dust. It also details an approach to the diagnosis, evaluation and management of this group of illnesses.

    10. Page 287
      Correspondence: V. Cottin, Hôpital Louis Pradel, 69677 Lyon (Bron) Cedex, France. E-mail:

      Because the lung manifestations of drugs may be highly variable, a high index of suspicion is required. Both current and past drug intake should be carefully evaluated in any patient with infiltrative lung disease. Drug-induced infiltrative lung disease may manifest as variable clinical radiological patterns, including subacute or chronic interstitial pneumonia, pulmonary fibrosis, eosinophilic pneumonia (presenting as Löffler syndrome, or chronic or acute eosinophilic pneumonia), organising pneumonia, diffuse alveolar haemorrhage, acute respiratory distress syndrome, pulmonary oedema, lipoid pneumonia, alveolar proteinosis or sarcoidosis. A variety of drugs have been incriminated, including those used in cardiovascular diseases (amiodarone, statins and angiotensin-converting enzyme inhibitors), antibiotics (especially minocycline and nitrofurantoin), most anticancer drugs and especially chemotherapy, treatment of rheumatoid arthritis (nonsteroidal anti-inflammatory agents, methotrexate, d-penicillamine and tumour necrosis factor-α inhibitors), as well as more recent drugs (interferon, interleukin-2, rituximab, imatinib, dasatinib, gefitinib and sirolimus). Although some risk factors have been identified, the precise mechanisms of drug-induced infiltrative lung disease are largely unknown. The history of exposure to the drug, the timing of drug exposure, the clinical and imaging pattern, the possible improvement following drug discontinuation and the exclusion of other causes of infiltrative lung disease all contribute to the diagnosis and assessment of causality. Although the recurrence of manifestations after patient rechallenge with the drug is considered the best imputability criterion, rechallenge may be dangerous and is discouraged. Web-based updated lists of drugs causing lung adverse events ( represent a useful tool when considering possible causative drugs, and drug causality should be carefully evaluated both in published cases and in clinical practice. Withdrawal of the offending drug and administration of corticosteroids when required may reverse a potentially life-threatening situation.

    11. Page 319
      Correspondence: A. Bush, Dept of Paediatric Respiratory Medicine, Royal Brompton Hospital, Sydney Street, London, SW3 6NP, UK. E-mail:

      Interstitial lung disease in children (chILD) is rare, and shows age-related differences in nature. In children aged 0–2 yrs, it is classified into diffuse developmental disorders; growth abnormalities reflecting deficient alveolarisation; specific disorders of undefined aetiology (pulmonary interstitial glycogenosis, neuroendocrine cell hyperplasia of infancy); surfactant dysfunction disorders; disorders of the normal host, presumed immune intact; disorders resulting from systemic processes; disorders of the immunocompromised host; and disorders masquerading as chILD. In older children (aged 2–16 yrs) the classification is less well worked out: immune-mediated, often systemic disease, infective and post-infective disease is more common. There are a large number of rare genetic conditions, which may also present in adult life; the same genetic disease may cause many different histological appearances, which may be age related.

      Presentation is usually nonspecific, and a systematic protocol of investigation is necessary. The presence of chILD is usually confirmed by high-resolution computed tomography, and the severity is determined by physiological tests. Although less invasive testing, such as surfactant protein genetics, may be diagnostic, most will need to proceed to a surgical lung biopsy for definitive diagnosis. Precise diagnosis is important, because of the genetic implications for some families and also because increasingly there are specific cytokine-targeted therapies, e.g. rituximab and etanercept, which are being used for specific indications.

      There are no randomised controlled trials of treatment in chILD. Oxygen therapy for the hypoxaemic, while spontaneous recovery occurs, may be all that is necessary, but many will need steroid therapy (pulse methyl prednisolone or oral prednisolone), which may be combined with hydroxychloroquine. There is even less evidence for the use of cytotoxic therapies such as methotrexate, azathioprine and cyclosporin. International collaborations, with protocol-driven evaluation of chILD, are urgently required if evidence-based treatment is to be determined.

    1. Page 357
      Correspondence: Z.F. Udwadia, P.D. Hinduja National Hospital and Medical Research Centre, Veer Savarkar Marg, Mahim, Mumbai 400016, India. E-mail:

      Interstitial lung diseases are a group of diffuse parenchymal lung diseases (DPLDs) that result from damage to the lung parenchyma by varying patterns of inflammation and fibrosis. There is limited data regarding the spectrum of DPLD from the Indian subcontinent. In this chapter, we have attempted to portray the salient epidemiological features, aetiological factors, clinical parameters, diagnostic delays, differential diagnosis and difficulties encountered in treatment of DPLD in a resource-limited setting like India.

      We have emphasised the reasons for the diagnostic delays in this condition in India. These include the overlap with other much more common and endemic conditions like tuberculosis and tropical pulmonary eosinophilia, and the nonavailability and cost of specialised investigations like high-resolution computed tomography, 6-min walking testing, diffusion capacity and video-assisted thoracoscopic surgery.

      Treatment of DPLD remains elusive in India, as in the West, and considerable controversy still exists as to when and how the current treatment with immunosuppressive agents should be used. Although lung transplant has been associated with improved lung function, exercise capacity, quality of life and survival in this group of patients, lung transplant is still in its infancy in India.

      The way ahead involves increasing awareness and interest amongst physicians, pulmonologists, radiologists and pathologists and establishing country-wide centres of excellence with a special interest in these fascinating but neglected (orphan) lung diseases.

    2. Page 375
      Correspondence: D.S. Kim, Dept of Pulmonary and Critical Care Medicine, Asan Medical Center, University of Ulsan, College of Medicine, 388-1 Poongnap-dong, Songpa-ku, Seoul, Korea. E-mail:

      Due to the paucity of the reports on interstitial lung disease (ILD) in the Far East, this chapter has focused on Korea and Japan.

      In Korea, the prevalence of ILD is not high; in particular, sarcoidosis is very rare in Korea. However, all Koreans are covered by the national health insurance, and medical expenses in Korea are much cheaper than in Western countries. Most big hospitals are fully equipped with highly technological tools and have qualified medical personnel; therefore, there is little difficulty in application of the American Thoracic Society/European Respiratory Society guidelines for ILD at the university or university-affiliated hospital level. However, the clinical burden on the physicians is much higher than in the West, resulting in ILD assuming a much lower priority and interest for the overworked pulmonologist. The shortage of ILD-specialist pathologists is a significant problem. Another characteristic feature is the high individual concern for health and performance of annual general medical check-ups, including computed tomography, before any symptoms appear, enabling of detection of early stages of disease.

      In Japan, the Specified Disease Treatment Research Program for various intractable diseases was set up in 1972, funded by grants from the Ministry of Health and Welfare. The Specified Disease Treatment Research Program for sarcoidosis was organised in 1972, and that for pulmonary fibrosis in 1973. These research groups have developed into combined groups, for example the granulomatous diseases group in 1978, the ILD group in 1980, the sarcoidosis, idiopathic interstitial pneumonia (IIP) and diffuse panbronchiolitis (DPB) group in 1982, the diffuse lung diseases (sarcoidosis, IIP and DPB) in 1988, and finally, the research groups for pulmonary diseases (diffuse lung diseases and pulmonary insufficiency) in 1996. This Specified Disease Treatment Research Program stimulated many pulmonary physicians to retain ILD as their area of specialist interest in terms of clinical research and practice throughout Japan. In 1995, the total number of patients registered with sarcoidosis was 13,008 (from 1974–1995), and for IIP it was 1,342 (in 1995). Additionally, the diagnostic problems and treatment issues, focused on characteristic aspects found in Japan, have been introduced.

    3. Page 386
      Correspondence: M. Conron, Dept of Respiratory Medicine, St Vincent's Hospital, P.O. Box 2900, Fitzroy, Victoria 3065, Australia. E-mail:

      Guideline-based clinical practice is increasingly seen as the preferred model of medical care. Despite the uptake of guidelines in other areas, their use in the investigation and management of interstitial lung disease (ILD) has not been widely accepted, due in part to the absence of well conducted studies to support recommendations.

      In this chapter, the value of a consistent guideline-based approach to the investigation and treatment of ILD despite a limited evidence base and lack of consensus about best practice is outlined. In particular, it is highlighted why it is necessary to accurately classify ILDs potentially responsive to treatment and to be able to identify patients with progressive disease. For patients with progressive ILD, enrolment in clinical trials and early referral to lung transplantation services are the interventions most likely to improve outcome.

      To be clinically useful, ILD guidelines must recognise that the preferred model of care is multidisciplinary and incorporate recommendations based on current evidence, using standardised terminology and consistent classification. To provide the necessary framework for clinicians to base patient care upon, guidelines must present and grade the evidence upon which recommendations are based. There are few strong recommendations made in ILD guidelines, due to the lack of well conducted clinical trials. As a result of this lack of evidence to support clinical practice, guideline development that uses novel methodology to support recommendations may be most appropriate. A system that allows a strong recommendation even when the evidence is weak, if it is deemed important, may assist clinical decision making.