TBLB is not recommended as the initial biopsy option in cases of suspected IPF and is unreliable in the diagnosis of rare lung disease (other than PAP)
BAL is not required as a diagnostic tool in patients with clinical features and HRCT appearances typical of IPF
EPIDEMIOLOGY OF IPF Incidence and Prevalence Prevalence of 20.2 cases per 100,000 for males and 13.2 cases per 100,000 for females Incidence has been estimated at 10.7 cases per 100,000 per year for males and 7.4 cases per 100,000 per year for females
POTENTIAL RISK FACTORS FOR IPF Cigarette Smoking Exposure to Commonly Prescribed Drugs Chronic Aspiration Environmental Factors Infectious Agents Genetic Predisposition to IPF. Familial IPF (FPF) is defined as at least two members of a primary biological family (parent, child, sibling) having clinical features of IPF that are confirmed histologically
Familial IPF Clinical findings, histopathology, and clinical course are indistinguishable between familial IPF and sporadic cases. Patients with familial IPF may be younger at diagnosis, but are otherwise indistinguishable from nonfamilial cases. IPF in families may be far more common than the 2% estimate that is currently reported, perhaps even 10-fold higher. The identification of the genetic basis of IPF in families may be the most effective method to identify the central pathogenetic features of IPF.
IDIOPATHIC PULMONARY FIBROSIS AND FAMILIAL PULMONARY FIBROSIS SURFACTANT PROTEIN C MUTATIONS AND LUNG FIBROSIS Interleukin-1 1 Receptor Antagonist and Tumor Necrosis Factor-α Complement Receptor 1 Surfactant Proteins A and B Angiotensin Converting Enzyme Transforming Growth Factor-1 Telomerase Mutations in Families with Idiopathic Pulmonary Fibrosis
Combined pulmonary fibrosis and emphysema (CPFE) A specific entity/syndrome? OR A subgroup of IPF with different prognosis? The diagnosis is based on findings of HRCT of the chest, which show either centrilobular emphysema or upper-zone bullous emphysema, associated in 90% of cases with very suggestive paraseptal emphysema and diffuse infiltrating fibrosing lung disease at the bases (subpleural reticular opacities, honeycomb images traction bronchiectasis)
Tobacco smoking Severe dyspnea CPFE Unexpected subnormal spirometry findings / preserved lung volumes Severely DLCO Hypoxemia at exercise Characteristic imaging features High probability of severe PAH PFTs may not be reliable for follow up of patients with CPFE
Cottin et al, Eur Respir J 2005 Lung volumes were normal in 42 out of 56 patients (75%) DLCO is markedly impaired The prevalence of pulmonary hypertension is particularly high in patients with CPFE Median survival was 6.1 yrs, a better survival than that reported in large studies of biopsy-proven UIP, but worse than emphysema alone
The prognosis of CPFE patients was better than that of IPF-alone patients The yearly decrease in VC and TLC of patients with CPFE is less than that of patients with IPF alone
CPFE 1) higher decrease in oxygen saturation during rest and exercise 2) a higher fibrosis HRCT scan score 3) a higher espap 4) lower median survival time IPF alone n=79 CPFE n=31 This dire prognosis seems to be at least partially associated with the development of severe pulmonary arterial hypertension
Natural History of the Clinical Progression of IPF The traditional view of IPF progression holds that a slow and steady decline in respiratory function ultimately leads to respiratory failure and death. Emerging evidence, however, has suggested that multiple injuries, or hits,, to the lung occur over a period of time, and these hits lead to acute exacerbations that result in periods of more rapid decline in lung function, which can ultimately result in death.
An n acute, clinically significant deterioration of unidentifiable cause in a patient with underlying IPF Only a subset of patients with IPF appears to develop acute exacerbations erbations
IPF is the most common form of IIP No therapy has been proven effective, and median survival from the time of diagnosis is approximately 3yrs Lung transplantation, which appears to improve survival in a subset of IPF patients, remains the only intervention. The natural history of IPF has been characterized as a steady, predictable decline in lung function over time. Some patients may experience a more precipitous course,, with periods of relative stability followed by acute deteriorations in respiratory status. Many of these acute deteriorations are of unknown etiology and have been termed acute exacerbations of IPF.
These studies are primarily retrospective case series and provide discordant estimates of incidence and mortality rates. The risk of an exacerbation does not appear to be linked to the level l of PFTs derangement, although in one series, patients with lower FVC had more hospitalizations during subsequent follow-up.
Diagnostic Criteria Previous or concurrent diagnosis of IPF Unexplained worsening or development of dyspnea within 30 days HRCT with new bilateral ground-glass glass abnormality and/or consolidation superimposed on a background consistent with UIP pattern No evidence of pulmonary infection by endotracheal aspirate or BAL Exclusion of alternative causes,, including the following: Left heart failure Pulmonary embolism Identifiable cause of acute lung injury
POTENTIAL ETIOLOGY 1. Acute exacerbations of IPF represent a distinct, pathobiological manifestation of the primary disease process, characterized by idiopathic lung injury 2. Acute exacerbations of IPF may represent clinically occult but biologically distinct conditions that go undiagnosed (e.g., viral infection, aspiration) 3. Acute exacerbations of IPF may be the sequelae of an acute direct stress to the lung,, with a subsequent acceleration of the already abnormal fibroproliferative process intrinsic to IPF
Endotracheal aspirate or BAL investigation is recommended (infectious etiology??) Routine studies for bacterial organisms, opportunistic pathogens (e.g., Pneumocystis jiroveci), and common respiratory viruses. Although the epidemiology of viral respiratory infections varies globally, relevant viruses in North America would include influenza A and B, parainfluenza 1 4, respiratory syncytial virus A and B, human metapneumovirus, adenoviruses, rhinovirus, and coronaviruses. Nosocomial infection?