The HRCT pattern in IPF includes patchy, peripheral, sub-pleural, bibasal reticular abnormalities with minimal ground-glass opacity. With advanced disease, honeycomb lung and traction bronchiectasis/bronchiolectasis, indicating end-stage lung fibrosis, are seen. Extensive areas of ground-glass haziness, indicating an acinar filling process, are not characteristic of IPF but may be seen in AIP, LIP, DIP/RBILD, and NSIP/F.
Pulmonary function testing The physiologic abnormalities of IPF are basically the same as those described for diffuse infil-trative lung disease. The classic composite physiologic picture of IPF is reduced DLCO, restriction of lung volume, exercise-induced oxygen desaturation, and absence of airflow obstruction. Some of the alterations correlate with the pathologic findings.
A diagnosis of IPF is established by correlating histopatho-logic and clinical findings. Clinically, IPF is suspected when a diffuse infiltrative lung disease occurs with no involvement of other organ systems and there is no apparent relation to infection, environmental exposure, or drugs. The chest radiograph shows no evidence of hilar adenopathy or pleural effusion. Laboratory tests in IPF are generally unrevealing, except for the presence of a positive antinuclear antibody or positive rheumatoid factor in up to 50% of cases. Thus, serum antinuclear antibody and rheumatoid factor cannot be relied on to differentiate IPF from diffuse infiltrative lung disease associated with collagen vascular disorders if the titers are low.
The initial approach to diagnosing IPF is to exclude as many causes of diffuse infiltrative lung disease as possible by a combination of history and clinical examination. However, a number of causes remain that cannot be reliably identified without a lung biopsy. Such causes include stage III sarcoidosis, lymphan-gitic carcinomatosis, lymphangioleiomyomatosis, eosinophilic granuloma, DIP/RBILD, NSIP/F, LIP, AIP, and the more diffuse forms of BOOP.
Imaging studies The radiographic features are nonspecific and most often consist of a bilateral reticular or reticulonodular pattern that typically appears in the lower lung fields; if cor pulmonale develops, enlargement of the pulmonary arteries and hypertrophy of the right ventricle occurs. In as many as 10% of patients with symptomatic IPF, the chest radiograph may be entirely normal. Radiographic findings in patients with IPF are limited to the lung fields. Hilar lymphadenopathy or pleural effusion suggests a different cause of diffuse infiltrative lung disease.
Lung biopsy Transbronchial lung biopsy is a sensitive tool for diagnosing sarcoidosis and lymphangitic cancer and may reveal pathologic features suggestive of IPF (i.e., fibrosis and widened alveolar septa with scant inflammatory cell infiltrate). Open lung biopsy is needed to exclude other causes of diffuse disease. It is up to the clinician to decide whether to proceed to open lung biopsy when clinical evaluation and transbronchial lung biopsy are highly suggestive of IPF. Open lung biopsy is advisable when there is any doubt about whether there is an infectious cause. Open lung biopsy should usually be performed in younger patients to establish the diagnosis of the underlying disorder with a reasonable degree of certainty.5 Older patients with typical clinical features and a compatible trans-bronchial lung biopsy result may reasonably be spared the morbidity associated with open lung biopsy. In certain cases, it may be reasonable to diagnose IPF without any tissue biopsy.
LIP is an interstitial lung disease characterized by diffuse or localized lymphocytic infiltration of the alveolar and interstitial areas of the lung.43,65 This disorder can occur in association with a number of autoimmune processes (especially Sjogren syndrome), dysproteinemias, immunodeficiency (AIDS and common variable immunodeficiency), drug reactions (e.g., to phenytoin), or bone marrow transplantation; or it can occur as an idiopathic process.
It suggests that genetic factors (eg, airway hyperresponsiveness [AHR] and atopy), endogenous factors (eg, sex and age), and exogenous factors (eg, allergens, infections, and smoking) all play a role in the pathogenesis of chronic nonspecific lung disease.
Genome-wide analysis on the Dutch hypothesisAU - Smolonska,JoannaAU - Koppelman,Gerard H.AU - Wijmenga,CiscaAU - Vonk,Judith M.AU - Zanen,PieterAU - Bruinenberg,MarcelAU - Curjuric,IvanAU - Imboden,MedeaAU - Thun,Gian AndriAU - Franke,LudeAU - Probst-Hensch,Nicole M.AU - Nürnberg,PeterAU - Riemersma,Roland A.AU - Van Schayck,Constant P.AU - Loth,Daan W.AU - Brusselle,Guy G.AU - Stricker,Bruno H.AU - Hofman,AlbertAU - Uitterlinden,André G.AU - Lahousse,LiesAU - London,Stephanie J.AU - Loehr,Laura R.AU - Manichaikul,AniAU - Graham Barr,R.AU - Donohue,Kathleen M.AU - Rich,Stephen S.AU - Pare,PeterAU - Bossé,YohanAU - Hao,KeAU - Van Den Berge,MaartenAU - Groen,Harry J.M.AU - Lammers,Jan Willem J.AU - Mali,WillemAU - Marike Boezen,H.AU - Postma,Dirkje S.PY - 2014/1/1Y1 - 2014/1/1N2 - Asthma and chronic obstructive pulmonary disease (COPD) are thought to share a genetic background (''Dutch hypothesis'').
NSIP/F occurs in middle-aged adults, with a mean age at onset of 49 years, but it can also affect children and older adults. There is a slight female predominance. Although some cases are idiopathic, many patients have collagen vascular diseases or immunodeficiency (including HIV infection), and some have a history of environmental or therapeutic drug exposures. A few patients have a history of an acute lung injury, such as that caused by pneumonia, ARDS, or surgery.
Three loci showed potential involvement in both diseases: chr2p24.3, chr5q23.1 and chrl3q14.2, containing DDX1, COMMD10 (both participating in the nuclear factor (NF) kappa beta pathway) and GNG5P5, respectively. Single nucleotide polymorphisms (SNPs) rs9534578 in GNG5P5 reached genome-wide significance after first replication phase (p=9.96 x 10(-9)). The second replication phase, in seven independent cohorts, provided no significant replication. Expression quantitative trait loci (eQTL) analysis in blood cells and lung tissue on the top 20 associated SNPs identified two SNPs in COMMD10 that influenced gene expression.
Figure 9 Desquamative interstitial pneumonia/respiratory bronchiolitis interstitial lung disease. The alveoli and septal walls are filled with macrophages, and no fibrosis is apparent.