Review series: Aspects of interstitial lung disease: connective tissue disease-associated interstitial lung disease: how does it differ from IPF? How should the clinical approach differ?

The lung is frequently involved in connective tissue diseases (CTDs), although the frequency of lung manifestations varies according to the type of CTD. Interstitial lung diseases (ILD) are frequently seen in CTDs, particularly systemic sclerosis (SSc), polymyositis/dermatomyositis (PM/DM) and rheumatoid arthritis (RA), accounting for a significant proportion of deaths. A large percentage of patients with CTD-associated ILD has limited and stable disease, not requiring treatment. However, a significant minority has severe and/or progressive disease, necessitating prompt initiation of treatment. CTD-ILD histological patterns include non-specific interstitial pneumonia (NSIP), usual interstitial pneumonia (UIP), organizing pneumonia (OP), diffuse alveolar damage (DAD) and lymphocytic interstitial pneumonia (LIP). NSIP is the most common pattern in all CTDs, except for RA, characterized by a higher frequency of UIP. ILD can present acutely or chronically, with acute presentations being more common in systemic lupus erythematosus and PM/DM. Idiopathic pulmonary fibrosis (IPF) is a progressively worsening ILD characterized by inflammation and fibrosis. The characteristic histological pattern of IPF is UIP. Interestingly, a UIP pattern is associated with a significantly better survival in CTD-related disease compared to the idiopathic variety. Prognosis in IPF is dismal, with a median survival since diagnosis of 2-3 years. No treatment regimen has been shown to improve survival in IPF. By contrast, although there have been only two randomized placebo-controlled trials investigating the effect of immunosuppressive treatment in SSc-associated ILD, clinical experience suggests that immunosuppressive drugs in CTD-related ILDs are capable of benefiting a significant proportion of patients, particularly those with certain histological patterns of disease. This review will essentially focus on CTD-associated ILD and will compare aspects of clinical presentation and management to those of IPF

Pleuroparenchymal fibroelastosis in systemic sclerosis: prevalence and prognostic impact

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Functional associations of pleuroparenchymal fibroelastosis and emphysema with hypersensitivity pneumonitis

BACKGROUND: Pleuroparenchymal fibroelastosis (PPFE) has been described in hypersensitivity pneumonitis (HP) yet its functional implications are unclear. Combined pulmonary fibrosis and emphysema (CPFE) has occasionally been described in never-smokers with HP, but epidemiological data regarding its prevalence is sparse. CTs in a large HP cohort were therefore examined to identify the prevalence and effects of PPFE and emphysema. Methods: 233 HP patients had CT extents of interstitial lung disease (ILD) and emphysema quantified to the nearest 5%. Lobar percentage pleural involvement of PPFE was quantified on a 4-point categorical scale: 0 = absent, 1 = affecting 33%. Marked PPFE reflected a total lung score of ≥3/18. Results were evaluated against FVC, DLco and mortality. RESULTS: Marked PPFE prevalence was 23% whilst 23% of never-smokers had emphysema. Following adjustment for patient age, gender, smoking status, and ILD and emphysema extents, marked PPFE independently linked to reduced baseline FVC (p = 0.0002) and DLco (p = 0.002) and when examined alongside the same covariates, independently linked to worsened survival (p = 0.01). CPFE in HP demonstrated a characteristic functional profile of artificial lung volume preservation and disproportionate DLco reduction. CPFE did not demonstrate a worsened outcome when compared to HP patients without emphysema beyond that explained by CT extents of ILD and emphysema. CONCLUSIONS: PPFE is not uncommon in HP, and is independently associated with impaired lung function and increased mortality. Emphysema was identified in 23% of HP never-smokers. CPFE appears not to link to a malignant microvascular phenotype as outcome is explained by ILD and emphysema extents

The role of gastro-esophageal reflux (GER) in systemic sclerosis and lung fibrosis

Systemic sclerosis (SSc) is an autoimmune condition characterized by tissue fibrosis of the skin and internal organs. A significant subgroup of SSc patients develops progressive interstitial lung disease(ILD) leading to pulmonary fibrosis similar to IPF (idiopathic pulmonary fibrosis). Gastro-esophageal reflux (GER) has been suggested as a driving factor in the pathogenesis of both SSc-ILD and IPF. The esophagus is affected in 50-82% of patients with SSc. Gastric reflux may be liquid, gaseous, or particulate; acid or nonacid; distal (localized to the distal oesophagus) or proximal (reaching the proximal oesophagus and pharynx). Reflux to the proximal oesophagus, which is intuitively linked to microaspiration into the lungs, appears to be quite common in patients with ILD-SSc and IPF. Importantly, a significant proportion of GER reflux is asymptomatic. Concentration of pepsin and bile acids in broncho-alveolar lavage (BAL) and exhaled breath condensate (EBC) have been investigated as biomarkers of microaspiration in various respiratory diseases. The confirmation of a causative link of microaspiration in the genesis and progression of lung fibrosis would have a major impact in the management of ILD-SSc patients. It is likely that proteases such as pepsin, and not the acidity, are the primary target for future therapies. Potent inhibitors specific for proteases, e.g. pepstatin, are available and have been tested in phase-III clinical trials

CYP2E1PstI/RsaI polymorphism and interaction with tobacco, alcohol and GSTs in gastric cancer susceptibility: A meta-analysis of the literature.

Studies investigating the association between cytochrome P450 2E1 (CYP2E1) 5'-flanking region (PstI/RsaI) polymorphism and gastric cancer risk report conflicting results. The rationale for this meta-analysis was to determine whether CYP2E1*2 (c2) variant allele of CYP2E1 increases gastric cancer risk, especially by interacting with smoking, alcohol and other metabolic gene polymorphisms. Two investigators independently searched the Medline and Embase databases. A qualitative scoring of papers was applied to their evaluation. Authors of the identified papers were contacted to obtain data on the mentioned co-exposures. A measurement of the biological interaction among two putative risk factors was estimated by the attributable proportion (AP) due to interaction. We identified 13 case-control studies, which included 2066 gastric cancer cases and 2754 controls. Using the random effects model, we found no association between PstI/RsaI genotype and gastric cancer risk [odds ratio (OR) = 0.97 (95% confidence interval (CI): 0.79-1.18) for c2 allele carriers and OR = 1.36 (95% CI: 0.82-2.25) for c2 homozygotes compared with homozygotes wild-type]. When only high-quality scored studies were considered, a statistically significant increased risk appeared among Asians [OR = 1.50 (95% CI: 1.16-1.94) for c2 carriers and OR = 2.62 (95% CI: 1.23-5.57) for c2 homozygotes]. No interaction was detected between CYP2E1-smoking/alcohol (AP = 0), while an AP of 60% appeared for individuals both c2 homozygotes and glutathione S-transferase M1 (GSTM1) null compared with both homozygotes wild-type. This meta-analysis suggests that the CYP2E1 PstI/RsaI polymorphism may be a risk factor for gastric cancer in Asians, and that a synergic relation among GSTM1 and CYP2E1 may account for a proportion of gastric cancer cases

A case of bronchial aspiration of a foreign body in a healthy adult: misdiagnosed with asthma and resolved with flexible bronchoscopy

A case of bronchial aspiration of a foreign body in a healthy adult: misdiagnosed with asthma and resolved with flexible bronchoscop

Additional file 1 of A formula for predicting emphysema extent in combined idiopathic pulmonary fibrosis and emphysema

Supplementary Material

Mucins MUC5B and MUC5AC in Distal Airways and Honeycomb Spaces: Comparison among Idiopathic Pulmonary Fibrosis/Usual Interstitial Pneumonia, Fibrotic Nonspecific Interstitial Pneumonitis, and Control Lungs

Although the pathogenesis of idiopathic pulmonary fibrosis (IPF) remains elusive (1), one of the most intriguing aspects concerns the possible role of mucins. A strong association has been reported between the promoter polymorphism rs35705950 of MUC5B and the occurrence of familial/sporadic IPF (2–10), as well as with a more benign disease course (10, 11). Overexpression of MUC5B and of the other main airway mucin, MUC5AC, has been described in IPF lungs (12, 13), but the level of expression in other types of pulmonary fibrosis is unknown. In this study, we compare MUC5B and MUC5AC expression among IPF, idiopathic nonspecific interstitial pneumonitis (i-NSIP), systemic sclerosis–associated NSIP (SSc-NSIP), and control lungs. Some of the results of this study have been previously reported in the form of an abstrac

Serum interleukin 6 is predictive of early functional decline and mortality in interstitial lung disease associated with systemic sclerosis

16siBiomarkers of progression of interstitial lung disease (ILD) are needed to allow early therapeutic intervention in patients with scleroderma-associated disease (SSc-ILD).reservedmixedDe Lauretis, Angelo; Sestini, Piersante; Pantelidis, Panagiotis; Hoyles, Rachel; Hansell, David M; Goh, Nicole S L; Zappala, Christopher J; Visca, Dina; Maher, Toby M; Denton, Christopher P; Ong, Voon H; Abraham, David J; Kelleher, Peter; Hector, Laureen; Wells, Athol U; Renzoni, Elisabetta ADe Lauretis, Angelo; Sestini, Piersante; Pantelidis, Panagiotis; Hoyles, Rachel; Hansell, David M; Goh, Nicole S. L; Zappala, Christopher J; Visca, Dina; Maher, Toby M; Denton, Christopher P; Ong, Voon H; Abraham, David J; Kelleher, Peter; Hector, Laureen; Wells, Athol U; Renzoni, Elisabetta A