Fibrotic Idiopathic Interstitial Pneumonias Research Articles

Changes in the physical and affective dimensions of dyspnoea after a home-based pulmonary rehabilitation in fibrotic idiopathic interstitial pneumonias.

Our objective was to evaluate the short-, medium- and long-term benefits of home-based pulmonary rehabilitation (PR) on the physical and affective components of dyspnoea in people with fibrotic idiopathic interstitial pneumonias (f-IIPs). Anxiety and depressive symptoms, fatigue, health-related quality of life and exercise tolerance were also assessed. Data on 166 individuals with f-IIPs who enrolled in an 8-week home-based PR programme (weekly supervised 90-min session) were retrospectively analysed. Assessments included the Dyspnoea-12 (D-12) questionnaire, Hospital Anxiety and Depression Scale, Fatigue Assessment Scale, Visual Simplified Respiratory Questionnaire and 6-min stepper test, and were performed at home at short, medium (6 months) and long (12 months) term. Among the 166 individuals with f-IIPs who enrolled in PR, 75 (45%) and 91 (55%) participants had a diagnosis of idiopathic pulmonary fibrosis and fibrosing non-specific interstitial pneumonia, respectively, and 87 (52%) participants concluded a full year of follow-up. In the total group, both physical and affective components of dyspnoea were improved, at short, medium and long term, after PR. Overall, half of the participants reached the minimally important difference of 3 points of the D-12 questionnaire at the end of PR, and at the 6- and 12-month follow-ups. Anxiety and depressive symptoms, fatigue and health-related quality of life were also improved, while the short-term benefits in exercise tolerance were not maintained 1 year after PR. An individualised home-based PR programme resulted in short-, medium- and long-term improvements in both physical and affective components of dyspnoea assessed by the D-12 questionnaire.

Intravenous immunoglobulin for acute exacerbation of fibrotic idiopathic interstitial pneumonias.

Acute exacerbation (AE) of idiopathic pulmonary fibrosis (IPF) is a fatal condition with no established treatment. Intravenous immunoglobulin (IVIG) is a unique therapy with both anti-inflammatory and anti-infective effects. Therefore, we hypothesized that IVIG may have a positive effect on AE of interstitial pneumonia. This study aimed to determine the effect of IVIG in patients with AE of fibrotic idiopathic interstitial pneumonias (IIPs), including IPF. We retrospectively analyzed consecutive patients who were diagnosed with AE of fibrotic IIPs and treated with pulse corticosteroid therapy (methylprednisolone 500-1000 mg/day for 3 days) between April 2018 and May 2021 at Kagawa Rosai Hospital and KKR Takamatsu Hospital. This study included 52 patients with AE of fibrotic IIPs (IPF,41; fibrotic IIPs other than IPF,11). Thirteen patients received IVIG (5 g/day for 3-5 days) concurrently with pulse corticosteroid therapy. The remaining 39 patients were assigned to the control group. The survival rate on day 90 was significantly higher in the IVIG group than that in the control group (76.9% vs. 38.5%, p = 0.02). IVIG administration (odds ratio [OR], 0.11; 95% confidence interval [CI], 0.02-0.69; p = 0.02) and C- reactive protein (OR, 1.19; 95% CI, 1.06-1.33, p < 0.01) were independently associated with 90-day mortality. The results indicate that administration of IVIG may improve the survival of patients with AE of fibrotic IIPs. We are now conducting a prospective study to confirm the effect of IVIG on AE of IPF since May 2022 (jRCT1061220010).

A New Tool to Assess Quality of Life in Patients with Idiopathic Pulmonary Fibrosis or Non-specific Interstitial Pneumonia.

Background Quality of life (QoL) is significantly impaired in patients with pulmonary fibrosis, however reliable tools to assess QoL issues specific for this group of patients are still missing. We thus aimed to develop a new questionnaire called “Quality of life in patients with idiopathic pulmonary fibrosis” (QPF) to measure QoL in patients with fibrotic idiopathic interstitial pneumonias (IIP). Methods An item pool was created on the basis of a German expert group with support of patients suffering from pulmonary fibrosis. In a 1st step, this version of the questionnaire was completed by 52 patients with idiopathic pulmonary fibrosis (IPF) or non-specific interstitial pneumonia (NSIP). Following this, an item- and an exploratory factor analysis was carried out and a 2nd version created. In a multicenter validation study in a one-group pre-post design, the questionnaire was filled in by 200 patients with IIP (IPF = 190, iNSIP = 10) at 2 time points with an interval of 6 months. Cross-validation was carried out with the St. Georges Respiratory Questionnaire (SGRQ). Results The mean age of the patients was 71.0 years (50–90 years), 82.5 % were male. Item analysis revealed that most of Cronbach alpha and selectivity values of QPF-scales could be considered as sufficient (e. g. QPF-scale “condition” [alpha = 0.827], “impairment” [alpha = 0.882]). At scale level, there were significant differences in terms of a deterioration or improvement in the QPF-condition and QPF-breathlessness scales and also in the SGRQ-activity scale. Analysis of construct validation of QPF and SGRQ showed moderate correlations between both questionnaires. A deterioration in health status from the patient’s and doctorʼs perspective was seen in the scales “impairment”, “shortness of breath” and “health status” of the QPF. The QPF was able to detect a change in the patientʼs mood (“condition” scale) in the course of treatment. Conclusion This newly developed questionnaire maps the special needs of the patients well. The QPF is suitable for screening of quality of life as well as for supplementing the medical history and for monitoring the course of disease in fibrotic IIPs.

The Diagnosis of Hypersensitivity Pneumonitis and the Role of Lung Biopsy

Hypersensitivity pneumonitis (HP) refers to a collective noun of diffuse lung diseases encompassing some degree of bronchiolar and interstitial granulomatous inflammation that results from persistent inhalation exposure and consequent immune sensitization to a large potential diversity of (predominantly) organic antigens in predisposed individuals. In suspected cases of HP, forceps transbronchial lung biopsy (TBLB) has been traditionally performed on a case-by-case basis along with bronchoalveolar lavage. This option has been subject to some debate and its use is more restrained in the presence of a chronic fibrotic form of HP—where surgical lung biopsy is classically recommended in the face of the need for a more reliable differentiation from fibrotic idiopathic interstitial pneumonias. We intended to assess the diagnostic contribution of conventional TBLB in the combined multidisciplinary diagnosis of an HP patient cohort. A retrospective evaluation of all the diagnostic elements and level of confidence from all HP cases followed in an interstitial lung disease ILD outpatient clinic of a district hospital center (Centro Hospitalar do Baixo Vouga), from June 2015 to August 2019, and simultaneously evaluated in a multidisciplinary team discussion of the same hospital, comprising an interstitial lung disease dedicated lung physician, a chest radiologist, 2 rheumatologists, and a pathologist. We identified 78 patients (mean age: 70.5 y, interquartile range: 58.5 to 78.0) with a slight female predominance. Most of the patients (61.5%) had chronic/fibrotic HP. The most frequently identified inducing antigens were avian antigens in 59.0% of cases, followed by molds in 20.5%. Of the 72 patients who underwent bronchofibroscopy, 36.1% (n=26) conventional TBLB performed, predominantly in the segments of the right lower lobe with an average number of 3.9 biopsies (SD±1.4) accomplished per patient. In 50.0% of the cases submitted to TBLB, the biopsies showed representative material with histologic features (definite or supportive) which had some degree of contribution for the diagnostic discussion. Among the patients where TBLBs were not performed or whose results were found to be devoid of significant findings, 73.1% were still diagnosed as HP without the need for surgical video-assisted thoracoscopic lung biopsy/transbronchial lung cryobiopsy (VATS/TBLCB) on the grounds of other diagnostic elements; 15.4% of patients were diagnosed with HP after a VATS/TBLCB procedure. Lastly, around 11.5% of patients were considered to have an unacceptable risk for VATS/TBLCB but, on the basis of clinical, radiologic, and immunologic elements received a multidisciplinary provisional diagnosis still with a reasonable level of confidence. Regarding complications with TBLB, there were 2 cases of moderate bleeding (7.6%) and 1 pneumothorax (3.8%) that did not require drainage. Notwithstanding its limitations, TBLB can still have a role in the diagnostic workup of HP, namely in acute/inflammatory HP, adding definite or supportive histologic information for multidisciplinary discussion in up to 50% of cases. TBLB can augment diagnostic yield at the expense of only a minimal increase of risk, as it is a universally available technique that can be performed along with bronchoalveolar lavage. This has important implications, particularly in centers devoid of TBLCB, as a surgical biopsy can be avoided in approximately half of patients who are eventually diagnosed with HP.

Long-term evaluation of home-based pulmonary rehabilitation in patients with fibrotic idiopathic interstitial pneumonias.

BackgroundFew studies have examined the benefits of pulmonary rehabilitation in patients with fibrotic idiopathic pulmonary pneumonia (f-IIP). Here, we report the results of an observational study in routine clinical practice of home-based pulmonary rehabilitation for f-IIP patients.MethodsA total of 112 consecutive patients (61 with idiopathic pulmonary fibrosis and 51 with fibrotic nonspecific interstitial pneumonitis) were enrolled, of whom 65 had mild-to-moderate disease (forced vital capacity (FVC) ≥50% predicted and diffusing capacity of the lung for carbon monoxide (DLCO) ≥30% predicted) and 47 had severe disease (FVC <50% predicted and/or DLCO <30% predicted). The 2-month pulmonary rehabilitation programme consisted of a once-weekly visit with retraining, therapeutic education and psychosocial support. Patients were provided with an individualised action plan and were followed-up bimonthly for 12 months. Exercise tolerance (6-min stepper test (6MST)), mood (Hospital Anxiety and Depression Scale (HADS)) and quality of life (QoL) (Visual Simplified Respiratory Questionnaire (VSRQ)) were assessed before (T0), immediately after (T2), 6 months after (T8) and 12 months after (T14) the end of the pulmonary rehabilitation programme.Results6MST strokes, HADS Anxiety score and VSRQ score were each significantly improved at T2 (n=101), T8 (n=76) and T14 (n=62) compared with T0 values. The improvements in outcomes were not influenced by disease severity or subtype. Patients who completed the study had significantly better baseline FVC and DLCO values than those who did not.ConclusionsHome-based pulmonary rehabilitation provides long-term benefits in exercise tolerance, anxiety and QoL for patients with f-IIP. Pulmonary rehabilitation should be prescribed systematically as part of the therapeutic arsenal for these patients.

Prevalence and incidence of interstitial lung diseases in a multi-ethnic county of Greater Paris.

The objective of the study was to estimate the prevalence and incidence of interstitial lung diseases (ILDs) in Seine-Saint-Denis, a multi-ethnic county of Greater Paris, France.Patients with ILDs were identified between January and December 2012 by using several sources; all potentially involved medical specialists from public and private hospitals, community-based pulmonologists and general practitioners, and the Social Security system. Diagnoses were validated centrally by an expert multidisciplinary discussion.1170 ILD cases were reported (crude overall prevalence: 97.9/105 and incidence: 19.4/105/year). In the 848 reviewed cases, the most prevalent diagnoses were sarcoidosis (42.6%), connective tissue diseases associated ILDs (CTDs-ILDs) (16%), idiopathic pulmonary fibrosis (IPF) (11.6%), and occupational ILDs (5.0%), which corresponded to a crude prevalence of 30.2/105 for sarcoidosis, 12.1/105 for CTDs-ILDs and 8.2/105 for IPF. The prevalence of fibrotic idiopathic interstitial pneumonias, merging IPF, nonspecific interstitial pneumonia and cases registered with code J84.1 was 16.34/105 An adjusted multinomial model demonstrated an increased risk of sarcoidosis in North Africans and Afro-Caribbeans and of CTDs-ILDs in Afro-Caribbeans, compared to that in Europeans.This study, with a comprehensive recruitment and stringent diagnostic criteria, emphasises the importance of secondary ILDs, particularly CTDs-ILDs and the relatively low prevalence of IPF, and confirms that sarcoidosis is a rare disease in France.

Clinical impact of high-attenuation and cystic areas on computed tomography in fibrotic idiopathic interstitial pneumonias.

BackgroundQuantitative computed tomography (CT) analysis has been proposed as a means of objectively assessing fibrotic interstitial pneumonia (IP) including idiopathic pulmonary fibrosis (IPF). We investigated whether percentages of high-attenuation areas (HAA%) and cystic areas (CA%) quantified from CT images were useful as indices of fibrotic IP.MethodsCT images of 74 patients with fibrotic idiopathic interstitial pneumonias (IPF, 36; non-specific interstitial pneumonia, 9; unclassifiable idiopathic interstitial pneumonia, 29) were analyzed via in-house computer software, which automatically calculated HAA%, CA%, mean lung density (MLD), standard deviation of lung density (SD-LD), kurtosis, and skewness from CT attenuation histograms. These indices were compared in each instance with physiologic measures, visual fibrosis score, clinical diagnosis, radiologic CT pattern, and prognosis.ResultsHAA% correlated significantly with physiologic measures and visual fibrosis score to a moderate extent (%forced vital capacity, rs = −0.59; % carbon monoxide diffusion capacity, rs = −0.43; fibrosis score, rs = 0.23). Densitometric parameters (MLD, SD-LD, kurtosis, and skewness) correlated significantly with physiologic measures and fibrosis score (|rs| = 0.28-0.59). CA% showed no association with pulmonary functions but differed significantly between IPF and other interstitial pneumonias (IPs) (1.50 ± 2.41 % vs. 0.41 ± 0.80 %; P < 0.01) and between the definite usual interstitial pneumonia (UIP) pattern and other patterns (1.48 ± 2.38 % vs. 0.55 ± 1.19 %; P < 0.01). On univariate analysis, HAA%, MLD, SD-LD, kurtosis, skewness, fibrosis score, and definite UIP pattern all correlated with survival, with kurtosis alone identified as a significant predictor of mortality on multivariate analysis (hazard ratio = 0.67; 95 % CI, 0.44-0.96; P = 0.03).ConclusionCA% and HAA% are novel quantitative CT indices with differing properties in fibrotic IP evaluations. HAA% largely reflects physiologic impairments, whereas CA% corresponds with diagnosis and HRCT pattern. Of the CT indices examined, kurtosis constituted the strongest predictor of mortality.

Genome-wide association study identifies multiple susceptibility loci for pulmonary fibrosis

We performed a genome-wide association study in non-Hispanic white subjects with fibrotic idiopathic interstitial pneumonias (N=1616) and controls (N=4683); replication was assessed in 876 cases and 1890 controls. We confirmed association with TERT and MUC5B on chromosomes 5p15 and 11p15, respectively, the chromosome 3q26 region near TERC, and identified 7 novel loci (PMeta = 2.4×10−8 to PMeta = 1.1×10−19). The novel loci include FAM13A (4q22), DSP (6p24), OBFC1 (10q24), ATP11A (13q34), DPP9 (19p13), and chromosomal regions 7q22 and 15q14-15. Our results demonstrate that genes involved in host defense, cell-cell adhesion, and DNA repair contribute to the risk of fibrotic IIP.

High-Resolution CT Findings in Fibrotic Idiopathic Interstitial Pneumonias With Little Honeycombing: Serial Changes and Prognostic Implications

This retrospective study evaluates serial changes of lung abnormalities on high-resolution CT (HRCT) and clarifies prognostic determinants among CT findings in fibrotic idiopathic interstitial pneumonias (IIPs) with little honeycombing. We enrolled 154 patients with a histologic diagnosis of a fibrotic IIP (< 5% honeycombing on CT) who were followed clinically for at least 2 years. One hundred one patients had usual interstitial pneumonia (UIP) and 53 had fibrotic nonspecific interstitial pneumonia (NSIP). On baseline CT, the extent and distribution of lung abnormalities were visually assessed, and serial CT scans were evaluated with a follow-up period of at least 6 months (n = 132). Significant differences were noted in the extent of reticulation and ground-glass opacification (GGO) between the UIP and fibrotic NSIP groups (p < 0.001). On serial scans, honeycombing (5% in UIP and 3% in fibrotic NSIP; p = 0.08) and reticulation (3% in UIP and 8% in fibrotic NSIP; p = 0.03) progressed in extent and GGO (-2% in UIP and -10% in fibrotic NSIP; p = 0.009) decreased in extent. Overall extent of lesions increased in UIP (6%) and decreased in NSIP (-4%) (p = 0.04). On univariate and multivariate Cox proportional hazards analysis, the overall extent of parenchymal abnormalities was a prognostic factor predictive of poor survival duration. Even in cases of fibrotic IIP with little honeycombing, serial CT reveals an increase in the extent of honeycombing and reticulation and a decrease in extent of GGO. Overall extent of lung fibrosis on the baseline CT examination appears predictive of survival in fibrotic IIP with little honeycombing.

Do we need exercise tests to detect gas exchange impairment in fibrotic idiopathic interstitial pneumonias?

In patients with fibrotic idiopathic interstitial pneumonia (f-IIP), the diffusing capacity for carbon monoxide (DLCO) has been used to predict abnormal gas exchange in the lung. However, abnormal values for arterial blood gases during exercise are likely to be the most sensitive manifestations of lung disease. The aim of this study was to compare DLCO, resting PaO2, P(A-a)O2 at cardiopulmonary exercise testing peak, and oxygen desaturation during a 6-min walk test (6MWT). Results were obtained in 121 patients with idiopathic pulmonary fibrosis (IPF, n = 88) and fibrotic nonspecific interstitial pneumonias (NSIP, n = 33). All but 3 patients (97.5%) had low DLCO values (<LLN) whereas only 66.6% had low KCO; 42 patients (65%) exhibited resting hypoxemia (<75 mmHg); 112 patients (92.5%) exhibited a high P[(A-a)O2], peak (>35 mmHg) and 100 (83%) demonstrated significant oxygen desaturation during 6MWT (>4%). Interestingly 27 patients had low DLCO and normal P(A-a)O2, peak and/or no desaturation during the 6MWT. The 3 patients with normal DLCO also had normal PaO2, normal P(A-a)O2, peak, and normal oxygen saturation during 6MWT. Our results demonstrate that in fibrotic IIP, DLCO better defines impairment of pulmonary gas exchange than resting PaO2, exercise P(A-a)O2, peak, or 6MWT SpO2.

Detection of herpes simplex virus type-1 in patients with fibrotic lung diseases.

The current study intends to investigate i) the incidence of herpes viruses including Herpes Simplex Virus type-1 (HSV-1), Cytomegalovirus (CMV) and Human Herpes Virus -6, -7, -8 (HHV6, HHV7, HHV8) in two biological samples, bronchoalveolar lavage fluid (BALF) and lung tissue biopsy, in different forms of pulmonary fibrosis, and ii) the induction of molecular pathways involved in fibrosis by herpesvirus infection in primary cell cultures. PCR was employed for the detection of CMV, HHV6-8 and HSV-1 DNA in lung specimens (4 controls and 11 IPF specimens) and BALF pellet [6 controls and 20 fibrotic Idiopathic Intestitial Pneumonias (f-IIPs) samples: 13 idiopathic pulmonary fibrosis (IPF) and 7 nonspecific idiopathic interstitial pneumonia (NSIP)] samples. Among all herpesviruses tested, HSV-1 was detected in 1/11 (9%) specimens from IPF lung tissue and in 2/20 (10%) samples of f-IIPs BALF whereas the control group was negative. Primary cell cultures from BALF of patients with IPF and healthy controls were infected in vitro with wild-type HSV-1 virus and Real Time PCR was employed for the detection of gene transcription of specific axes implicated in lung fibrosis. Primary cell cultures were permissive to HSV-1, resulting in an upregulation of the fibrotic growth factors TGFβ1 and FGF, the angiogenetic markers SDF1a, SDF1b, VEGF, FGF and the regulators of tissue wound healing MMP9 and CCR7. Downregulation was noted for the CXCR4 and MMP2 genes, while a different response has been detected in healthy donors regarding the expression of the aforementioned markers. These results implicate for the first time the HSV-1 with Fibrotic Idiopathic Interstitial Pneumonias since the virus presented similar incidence in two different biological samples.

Fibrotic idiopathic interstitial pneumonias: HRCT findings that predict mortality

The study aims were to identify CT features that predict outcome of fibrotic idiopathic interstitial pneumonia (IIP) when information from lung biopsy data is unavailable. HRCTs of 146 consecutive patients presenting with fibrotic IIP were studied. Visual estimates were made of the extent of abnormal lung and proportional contribution of fine and coarse reticulation, microcystic (cysts ≤4 mm) and macrocystic honeycombing. A score for severity of traction bronchiectasis was also assigned. Using death as our primary outcome measure, variables were analysed using the Cox proportional hazards model. CT features predictive of a worse outcome were coarse reticulation, microcystic and macrocystic honeycombing, as well as overall extent of lung abnormality (p < 0.001). Importantly, increased severity of traction bronchiectasis, corrected for extent of parenchymal abnormality, was predictive of poor prognosis regardless of the background pattern of abnormal lung (HR = 1.04, CI = 1.03-1.06, p < 0.001). On bivariate Cox analysis microcystic honeycombing was a more powerful determinant of a poor prognosis than macrocystic honeycombing. In fibrotic IIPs we have shown that increasingly severe traction bronchiectasis is indicative of higher mortality irrespective of the HRCT pattern and extent of disease. Extent of microcystic honeycombing is a more powerful determinant of outcome than macrocystic honeycombing.

Fibrotic idiopathic interstitial pneumonias: Mortality is linked to a decline in gas transfer

Baseline clinical and physiological features and changes in these parameters over time are known predictors of survival in patients with fibrotic idiopathic interstitial pneumonia (IIP). Pulmonary hypertension is common in advanced fibrotic IIP, and has a negative impact on survival. Serial pulmonary function profiles, indicative of increasing vascular impairment in patients with IIP, and in particular, selective reductions in gas transfer, have not been studied previously. Predictors of event-free survival time were investigated in a cohort of Dutch patients with IPF and fibrotic non-specific interstitial pneumonia (n = 117). Pulmonary function test data were prospectively collected from November 1993 to December 2005. Multivariate Cox regression models were developed to identify the prognostic relevance to survival of variables related to baseline demographics, histopathology, pulmonary function and the 6- and 12-month changes in pulmonary function parameters. Different survival patterns were observed for patients with different histopathological diagnoses. At baseline, FVC was the most important prognostic factor. At the 6-month follow up, change in transfer coefficient (K(CO), DL(CO)/V(A)), and at the 12-month follow up, age, baseline K(CO) and 12-month change in FVC and K(CO), were independent predictors of event-free survival. Apart from histopathology, change in K(CO) over time appeared to be the most consistent and powerful predictor of survival in these patients. The decline in K(CO) may be indicative of increasing vascular impairment, which may have a major impact on survival, in patients with fibrotic IIP.

Upregulation of stromal cell derived factor-1α in collagen vascular diseases-associated interstitial pneumonias (CVDs-IPs)

Objective We speculated that distinct angiogenic profiles are involved in idiopathic interstitial pneumonias (IIPs) in comparison with interstitial pneumonias associated with collagen vascular disease (CVD-IPs). This hypothesis was investigated by measuring the expression of a cardinal biologic axis, the vascular endothelial growth factor (VEGF)–stromal derived growth factor [SDF-1α, transcripts 1 and 2 (TR1 and TR2)] and receptor, CXCR4 and the angiogenetic receptors CXCR2 and CXCR3 in bronchoalveolar lavage fluid (BALF) in both conditions. Methods We studied prospectively 25 patients with fibrotic IIPs (f-IIPs) [20 with idiopathic pulmonary fibrosis (IPF) and 5 with idiopathic non-specific interstitial pneumonia (NSIP)] and 16 patients with CVD-IPs. mRNA expression was measured by Real-Time RT-PCR and protein was evaluated by Western Blotting. Results A significantly greater value has been detected in SDF-1α-TR1 mRNA expression levels of CVD-IPs ( p = 0.05) in comparison with IPF group. A similar trend has been also detected in protein expression in favor of CVD-IP group. In addition, VEGF mRNA levels have been found significantly increased in CVD-IPs in comparison with the NSIP group ( p = 0.05). No significant difference has been found in SDF-1α-TR2–CXCR4 mRNA and CXCR2–CXCR3 between the two groups. Conclusion These results showed increased expression of SDF-1α in CVD-IPs, suggesting different angiogenic procedures. Further studies are needed in order to better explore the angiogenetic pathway in these disorders.

Prognostic Determinants among Clinical, Thin-Section CT, and Histopathologic Findings for Fibrotic Idiopathic Interstitial Pneumonias: Tertiary Hospital Study

To evaluate the utility of clinical, thin-section computed tomography (CT), and histopathologic findings in predicting the prognosis of patients with usual interstitial pneumonia (UIP) or fibrotic nonspecific interstitial pneumonia (NSIP). The institutional review board approved this retrospective study, with waiver of informed consent. Included were 108 patients (71 men, 37 women; mean age, 61 years +/- 8 [standard deviation]) with UIP (n = 79; 60 men, 19 women; mean age, 63 years +/- 7.4) and fibrotic NSIP (n = 29; 11 men, 18 women; mean age, 57 years +/- 12.9). Patients underwent pulmonary function tests (PFTs), bronchoalveolar lavage (BAL) fluid analysis, and thin-section CT. Two chest radiologists independently assigned scores for the extent of lung abnormalities detected at CT twice at 3-month intervals. The effect of histopathologic diagnoses and clinical and thin-section CT features on survival was evaluated by using Cox regression analyses. The 5-year survival rate (mean follow-up, 45 months) of patients with fibrotic NSIP was 76% in contrast to 46% for patients with UIP (P = .006). With multivariate analysis, a high fibrotic score (the extent of reticulation plus honeycombing) (hazard ratio = 1.200, P = .043) and an initial low diffusing capacity of lung for carbon monoxide (Dlco) level (hazard ratio = 0.973, P = .025) were identified as associated with increased death risk. Patients with UIP or fibrotic NSIP who have a high fibrotic score determined at thin-section CT and a low Dlco level appear to have a high death risk.

A double blind randomised placebo controlled pilot study of oral co-trimoxazole in advanced fibrotic lung disease

Background: In 1996, clinical improvement with oral co-trimoxazole was noted in a patient with biopsy proven advanced fibrotic lung disease who was awaiting a lung transplant. Subsequently, 14 patients with end stage fibrotic lung disease also responded to oral co-trimoxazole. This prompted a double blind randomised placebo controlled pilot study in patients with advanced stages of idiopathic interstitial pneumonias (IIP) to objectively measure benefit. Patients: Twenty patients (aged 49–84 years; 11 males) with progressive fibrotic lung disease who had differing subtype diagnosis from CT scans of progressive fibrotic IIP, and showed oxygen desaturation on exertion were selected. Method: A detailed assessment of arterial gases, lung function, and progressive shuttle-walking tests combined with oxygen saturation monitoring. Quality of life data was recorded. Randomisation was to co-trimoxazole or identical placebo for 3 months followed by 6 weeks of pulmonary rehabilitation before decoding. Placebo patients received active treatment upon decoding with continued follow up of all patients. Main outcome measures: Primary 1. Shuttle walking test. Secondary 2. FVC and quality of life. Results: Active treatment showed a significant improvement in shuttle walking test from 255 to 355 m ( p = 0.002 ) (95% CI 200–450) with reduced oxygen desaturations during exercise ( p = 0.003 ). FVC improved on treatment (+21%) from median 1.9 to 2.3 L ( p = 0.05 ) (95% CI 1.3–3.0) but TLC and DLCO were not significantly changed although stable at 12 months. The MRC 5 Point Dyspnoea Score showed improvement ( p = 0.05 ) at 3 months for the active group which was maintained at 12 months. The SGHRQ showed a significant reduction in symptom scores at 12 months ( p = 0.05 ). The placebo group showed no significant change in any parameters, but demonstrated identical improvement following oral co-trimoxazole. Serum vascular endothelial growth factor (VEGF) was reduced 50% in the active group at 3 months, but just failed to reach statistical significance. ‘Out of study’ HRCT scans in 12 patients showed significant reduction in ground glass changes ( p = 0.05 ) after 12 months of continuous co-trimoxazole treatment. Conclusion: The findings of the pilot study show significant improvements in objective and subjective parameters which fulfil the ATS/ERS (2000) criteria of ‘a favourable response to treatment’.

Fibrotic Idiopathic Interstitial Pneumonia: High-Resolution Computed Tomography Considerations

The fibrotic idiopathic interstitial pneumonias comprise usual interstitial pneumonia (UIP) and nonspecific interstitial pneumonia (NSIP). The characteristic high-resolution computed tomography findings of UIP are reticular abnormality and honeycombing with basal and peripheral predominance. Honeycombing is the strongest predictor of UIP. The extent of fibrosis on computed tomography (CT) is an important prognostic indicator in idiopathic pulmonary fibrosis (IPF). When ground-glass attenuation is seen in IPF it commonly progresses to fibrosis and honeycombing. Imaging may help to detect complications of IPF, including accelerated progression, lung cancer, and secondary infection. Our understanding of the clinical and radiological features of NSIP is still evolving. The CT finding of extensive ground-glass abnormality and some reticular abnormality, with basal and peripheral predominance, is strongly suggestive of NSIP. However, the CT appearances of NSIP overlap with those of UIP, organizing pneumonia (OP), and desquamative interstitial pneumonia (DIP), and biopsy may be necessary to sort this out. Other idiopathic pneumonias that may be associated with CT evidence of lung fibrosis include DIP, OP, acute interstitial pneumonia, and lymphoid interstitial pneumonia.