Idiopathic pulmonary fibrosis (IPF), the most lethal form of interstitial pneumonia of unknown cause, is associated with a specific radiological and histopathological pattern (the so-called “usual ...interstitial pneumonia” pattern) and has a median survival estimated to be between 3 and 5 years after diagnosis. However, evidence shows that IPF has different clinical phenotypes, which are characterized by a variable disease course over time. At present, the natural history of IPF is unpredictable for individual patients, although some genetic factors and circulating biomarkers have been associated with different prognoses. Since in its early stages, IPF may be asymptomatic, leading to a delayed diagnosis. Two drugs, pirfenidone and nintedanib, have been shown to modify the disease course by slowing down the decline in lung function. It is also known that 5–10% of the IPF patients may be affected by episodes of acute and often fatal decline. The acute worsening of disease is sometimes attributed to identifiable conditions, such as pneumonia or heart failure; but many of these events occur without an identifiable cause. These idiopathic acute worsenings are termed acute exacerbations of IPF. To date, clinical biomarkers, diagnostic, prognostic, and theranostic, are not well characterized. However, they could become useful tools helping facilitate diagnoses, monitoring disease progression and treatment efficacy. The aim of this review is to cover molecular mechanisms underlying IPF and research into new clinical biomarkers, to be utilized in diagnosis and prognosis, even in patients treated with antifibrotic drugs.
Abstract
Background
Sarcoidosis and hypersensitivity pneumonitis (HP) are two distinct clinical entities that share granulomatous inflammation, although each of them has specific clinical, radiologic ...and pathologic profiles. Coexistence of the two diseases have been described, suggesting, at least in some cases, a common biologic background.
Case presentation
We describe two patients showing the concurrent diagnosis of sarcoidosis and hypersensitivity pneumonitis. Case 1: a 51-year old never smoker man had a history of occupational exposure, episodes of acute exacerbations and positive serum precipitins to
Penicillium spp
suggestive of HP, while the positivity of serum angiotensin converting enzyme (ACE) favored sarcoidosis. Case 2: a 42-year old non-smoker woman with occasional finding of enlarged mediastinal lymph nodes had a history of domestic exposure to molds and positive serum precipitins to
Aspergillus spp
suggestive of HP.
In both cases high resolution computed tomography (HRCT) together with broncoscopy findings allowed to maintain both the diagnoses: HRCT showed both enlarged hilar/mediastinal limph nodes and intersitial lung involvement typical of HP; bronchoalveolar lavage presented marked lymphocytosis and granulomatous nodal lesions were observed at transbronchial needle aspiration.
Conclusions
Sarcoidosis and HP share some clinical findings and the differential diagnosis may be difficult. Our cases suggest that a common trait may be responsible for the concurrent diagnosis of sarcoidosis and hypersensitivity pneumonitis in the same patient.
During the past decades, a growing interest has been raised in evaluating nontuberculous mycobacteria (NTM) in patients with noncystic fibrosis bronchiectasis (NCFBE). This paper reviews several ...aspects of the correlations between NTM and NCFBE, including pathogenesis, radiological features, diagnosis, and management. Bronchiectasis and NTM lung disease are connected, but which one comes first is still an unresolved question. The rate of NTM lung disease in NCFBE varies through the studies, from 5% to 30%. The most frequent species isolated is MAC. NCFBE patients affected by NTM infection frequently present coinfections, including both other different NTM species and microorganisms, such as P. aeruginosa. Once a diagnosis of NTM disease has been reached, the initiation of therapy is not always mandatory. NTM species isolated, patients’ conditions, and disease severity and its evolution should be considered. Risk factors for disease progression in NCFBE patients with NTM are low body mass index, cavitary disease, consolidations, and macrolide resistance at presentation.
Chronic airway infection is a key aspect of the pathogenesis of bronchiectasis. A growing interest has been raised on non-tuberculous mycobacteria (NTM) infection. We aimed at describing the clinical ...characteristics, diagnostic process, therapeutic options and outcomes of bronchiectasis patients with pulmonary NTM (pNTM) disease. This was a prospective, observational study enrolling 261 adult bronchiectasis patients during the stable state at the San Gerardo Hospital, Monza, Italy, from 2012 to 2015. Three groups were identified: pNTM disease; chronic
infection; chronic infection due to bacteria other than
. NTM were isolated in 32 (12%) patients, and among them, a diagnosis of pNTM disease was reached in 23 cases. When compared to chronic
infection, patients with pNTM were more likely to have cylindrical bronchiectasis and a "tree-in-bud" pattern, a history of weight loss, a lower disease severity and a lower number of pulmonary exacerbations. Among pNTM patients who started treatment, 68% showed a radiological improvement, and 37% achieved culture conversion without recurrence, while 21% showed NTM isolation recurrence. NTM isolation seems to be a frequent event in bronchiectasis patients, and few parameters might help to suspect NTM infection. Treatment indications and monitoring still remain an important area for future research.
Interferon-gamma (IFN-gamma) release assays (IGRAs) were designed to detect latent tuberculosis infection (LTBI). However, discrepancies were found between the tuberculin skin test (TST) and IGRAs ...results that cannot be attributed to prior Bacille Calmètte Guerin vaccinations. The aim of this study was to evaluate tools for improving LTBI diagnosis by analyzing the IFN-gamma response to RD1 proteins in prolonged (long-term response) whole blood tests in those subjects resulting negative to assays such as QuantiFERON-TB Gold In tube (QFT-IT).
The study population included 106 healthy TST+ individuals with suspected LTBI (recent contact of smear-positive TB and homeless) consecutively enrolled. As controls, 13 healthy subjects unexposed to M. tuberculosis (TST-, QFT-IT-) and 29 subjects with cured pulmonary TB were enrolled. IFN-gamma whole blood response to RD1 proteins and QFT-IT were evaluated at day 1 post-culture. A prolonged test evaluating long-term IFN-gamma response (7-day) to RD1 proteins in diluted whole blood was performed.
Among the enrolled TST+ subjects with suspected LTBI, 70/106 (66.0%) responded to QFT-IT and 64/106 (60.3%) to RD1 proteins at day 1. To evaluate whether a prolonged test could improve the detection of LTBI, we set up the test using cured TB patients (with a microbiologically diagnosed past pulmonary disease) who resulted QFT-IT-negative and healthy controls as comparator groups. Using this assay, a statistically significant difference was found between IFN-gamma levels in cured TB patients compared to healthy controls (p < 0.006). Based on these data, we constructed a receiver operating characteristic (ROC) curve and we calculated a cut-off. Based on the cut-off value, we found that among the 36 enrolled TST+ subjects with suspected LTBI not responding to QFT-IT, a long term response to RD1 proteins was detected in 11 subjects (30.6%).
These results indicate that IFN-gamma long-term response to M. tuberculosis RD1 antigens may be used to detect past infection with M. tuberculosis and may help to identify additional individuals with LTBI who resulted negative in the short-term tests. These data may provide useful information for improving immunodiagnostic tests for tuberculosis infection, especially in individuals at high risk for active TB.
Diffuse alveolar haemorrhage (DAH) has been rarely reported in association with pulmonary infections.
We report the case of a 43 year old immunocompetent man presenting with dyspnoea, fever and ...haemoptysis. Chest imaging showed bilateral ground glass opacities. Microbiological and molecular tests were positive for Mycobacterium tuberculosis and treatment with isoniazid, rifampicin, ethambutol and pyrazinamide was successful. In this case the diagnosis of DAH relies on clinical, radiological and endoscopic findings. Routine blood tests documented the presence of anticardiolipin antibodies. In the reported case the diagnostic criteria of antiphospholipid syndrome were not fulfilled.
The transient presence of anticardiolipin antibodies in association with an unusual clinical presentation of pulmonary tuberculosis is intriguing although a causal relationship cannot be established.
Abstract Introduction The aim of this study is to compare characteristics of non-cystic fibrosis bronchiectasis (NCFBE) patients with chronic infections with non-tuberculous mycobacteria (NTM) versus ...those with Pseudomonas aeruginosa or other colonizations. Methods This was an observational, perspective study of consecutive NCFBE adult patients attending the outpatient bronchiectasis clinic at the San Gerardo Hospital in Monza, Italy, during 2012 and 2013. Patients with a chronic infection were included in the study and divided into three groups: those with NTM (Group A); those with P. aeruginosa (Group B); and those with other pathogens (Group C). Patients with both NTM and another pathogen were included in Group A. Comparison among the three study groups was performed using X2 or Fisher exact test for categorical variables or Kruskal–Wallis or Mann–Whitney test for continuous variables. Results A total of 146 patients (median age 67 years, 40% males) were enrolled: 19 belonged to Group A, 34 to Group B and 93 to Group C. Within group A, 6 patients had only NTM isolation, 7 patients had NTM and P. aeruginosa co-infection and 6 patients had NTM plus another pathogen. The most common isolated pathogens among NTM was Mycobacterium avium complex (15 patients, 79%). A total of 4 patients (21%) with NTM were on active treatment. Patients affected by NTM pulmonary infection had a significantly less severe clinical, functional and radiological involvement compared with patients colonized by P. aeruginosa , see Table. Group A (NTM) n = 19 Group B ( P. aeruginosa ) n = 34 Group C (Others) n = 93 p Value∗ p Value# p Value+ Age (years), median (IQR) 70 (64–75) 74 (67–79) 66 (53–72) 0.001 0.172 0.050 Male, n (%) 8 (42) 15 (44) 36 (33) 0.660 – – BMI, median (IQR) 22 (19–26) 24 (21–25) 24 (21–27) 0.352 – – BSI, median (IQR) 5 (4–9) 12 (8.5–16) 5 (3–7) 0.001 0.001 0.090 Bhalla score, median (IQR) 21 (15–34) 36 (30.5–40.5) 16 (10.5–21.5) 0.001 0.016 0.076 Idiopathic etiology, n (%) 8 (42) 11 (32) 37 (40) 0.721 – – Post-infective etiology, n (%) 8 (42) 16 (47) 29 (31) 0.244 – – Exacerbations/y, median (IQR) 1 (0–2) 2 (1.5–3.5) 2 (1–2) 0.040 0.024 0.132 FEV1%, median (IQR) 85 (59.75–109.5) 58.5 (48.25–74) 84 (62–102) 0.002 0.010 0.857 FVC%, median (IQR) 94.5 (70–109.75) 65 (56–81.5) 88 (69.5–101.5) 0.003 0.003 0.270∗ Among the three groups:# Group A vs. Group B;+ Group A vs. Group C; BMI: Body mass index; BSI: bronchiectasis severity index; y: year. Conclusions Colonization with P. aeruginosa seems to have the highest impact on the clinical, functional and radiological status of patients with NCFBE. No specific characteristics may help to identify NTM versus other pathogen colonizations. Thus, diagnostics for atypical mycobacteria should be performed on all patients with NCFBE, as suggested by recent international guidelines.
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