I. Definition of interstitial pulmonary fibrosis (IPF).
Interstitial pulmonary fibrosis (IPF) is a specific form of chronic, progressive fibrotic interstitial pneumonia of unknown cause, confined to the lungs. Its etiology is unknown, it occurs mainly in the elderly, and its histologic and/or imaging presentation is UIP.
II. On epidemiology.
Although there are still no large-scale epidemiological studies on IPF, the incidence of IPF shows a clear trend of increase. A study based on the population of Bernalillo County, New Mexico, USA: the incidence of IPF was estimated to be 10.7/100,000/yr. in men; 7.4/100,000/yr. in women. A British study reported an overall IPF incidence of 4.6/100,000/yr. from 1991 to 2003, with an estimated 11% annual increase in IPF incidence, which was not associated with an aging population or an increase in the diagnosis of mild cases. A third study from a large U.S. health plan estimated the incidence of IPF to be 6.8-16.3 per 100,000. Another study estimated the prevalence of IPF at 2-29 per 100,000 of the total population. The reasons for this wide variation in data across studies may be related to the lack of a uniform definition of IPF in the past, the design of individual studies, and differences in populations. A recent analysis of information from a large sample of health plans in the United States estimated the prevalence of IPF to be between 14.0 – 42.7 per 100,000. the difficulty in determining the prevalence of IPF is related to the influence of a variety of factors such as geography, country, culture or ethnicity.
Third, regarding the risk factors for IPF.
1. smoking: significantly increased risk for more than 20 packs per year.
2, environmental exposure: including metal dust, wood chips, farming, bird breeding, hair conditioner, stone dust exposure, livestock exposure, plant and animal dust exposure, etc.
3, microbial factors: including viral infections, of which EBV and hepatitis virus are more frequently reported in studies. Others are cytomegalovirus, human herpes virus, etc.
4. Gastro-esophageal reflux: Most patients with IPF lack clinical symptoms of gastro-esophageal reflux and are therefore easily overlooked.
The new guidelines emphasize that there are no relevant genetic tests available to distinguish familial or sporadic IPF; the interaction between genetic and environmental factors requires more research.
1. Familial IPF: < 5% of all patients. They may have an earlier onset, and the different genotypes may be related to the geographical distribution of patients. A group of Finnish case studies suggested that an ELMOD2 gene of unknown function was found on chromosome 4q31, which was analyzed as a possible susceptibility gene for familial IPF. Some studies suggest that IPF is linked to chromosome 14. Multiple studies have strongly suggested that mutations in the SP-C gene are associated with familial IIP, but no association with disseminated cases has been found. Rare mutations in the gene encoding SP-A2 protein have been associated with familial pulmonary fibrosis and lung cancer. Several recent reports demonstrate that genetic variations in human telomerase reverse transcriptase (hTERT) or human telomerase RNA occur in association with familial pulmonary fibrosis (15%), but also in some disseminated cases (3%), and that these genetic changes cause telomere shortening and eventually apoptosis (including alveolar epithelial cells).
2. Sporadic IPF: To date, no genetic factors have been consistently linked to sporadic IPF. Sporadic cases have been reported to have altered polymorphisms in several genes encoding cytokines, including, IL-1 a, TNF- a, lymphotoxin a, IL-4, IL-6, IL-8, IL-10 and IL-12, a1-antitrypsin and angiotensin converting enzyme, TGF- b1, coagulation factors, SP-A and B, immunomodulatory factors (complement receptor-1, NOD2/CARD15), MMP-1, etc. Many of these are associated with the progression of IPF, but none of these findings have been confirmed in subsequent studies. single phenotypes of HLA-I and class II antigen alleles are skewed in patients with IPF, with ethnic differences. Recent data from Mexico suggest an association of MHC-I with IPF.
V. Main points regarding diagnosis.
UIP used to refer exclusively to characteristic changes in the pathological histology of patients with IPF. The new guidelines propose for the first time that HRCT features based on UIP can be used as an independent diagnostic tool for IPF, thus greatly simplifying the new diagnostic criteria. Many studies have confirmed that the accuracy of HRCT in diagnosing UIP can reach 90% – 100%, so the new guidelines propose that pathological biopsy is not necessary for those with typical HRCT manifestations of UIP, thus abolishing the primary and secondary diagnostic criteria proposed in the 2000 ATS/ERS Consensus.
1. Diagnostic criteria for IPF.
a. Exclusion of other interstitial lung diseases (ILD) (e.g., home or occupational environmental exposure-related ILD, connective tissue disease-related ILD, and drug toxicity-related ILD).
b. Surgical lung biopsy is not recommended for those who exhibit UIP on high resolution CT (HRCT) (Appendix 1).
c. Atypical individuals (probable, suspected diagnosticians) are subject to lung biopsy (Annex 2).
2. The correctness of IPF diagnosis gradually increases with multidisciplinary discussions between pulmonary clinical specialists, imaging specialists and pathologists with experience in ILD diagnosis (Annex 3).
3, In younger patients, especially women, the clinical and serologic positive manifestations associated with connective tissue disease become progressively apparent as the disease progresses and may not be present at the beginning of the disease, and these patients (under 50 years of age) should be highly suspicious of connective tissue disease.
The majority of patients with IPF do not require TBLB and BAL examinations, and the purpose of TBLB and BAL examinations in a few atypical patients is mainly to exclude other diseases, which is not very helpful for the diagnosis of UIP.
5. Even if the patient lacks relevant clinical manifestations, serological examination of connective tissue disease should be routinely performed, and should be frequently reviewed during the follow-up, and the diagnosis should be changed once abnormalities are found.
6. About multidisciplinaryDiscussion (MDD): Many institutions cannot do formal MDD, but at least oral communication should be conducted.
VI. About treatment
For IPF, there is no definite effective drug treatment so far. The new guidelines change most treatments to recommendations of varying intensity.
Most patients with acutely exacerbated IPF should be treated with corticosteroids, but not for a few patients
Asymptomatic esophageal reflux, most should be treated, a few may be left untreated
Not recommended
glucocorticoids, colchicine, cyclosporine A, glucocorticoids + immunosuppressants, interferon (IFN)-γ1b, bosentan, etanercept
glucocorticoids + N-acetylcysteine + azathioprine, N-acetylcysteine alone, anticoagulants, pirfenidone, mechanical ventilation (the above measures may be tried in a few patients)
Combined pulmonary hypertension should not be treated in most patients with IPF, and may be treated in a few.