Severity Of Lung Impairment Research Articles

Effect of TB Treatment on Neutrophil-Derived Soluble Inflammatory Mediators in TB Patients with and without HIV Coinfection.

The mycobacteriological analysis of sputum samples is the gold standard for tuberculosis diagnosis and treatment monitoring. However, sputum production can be challenging after the initiation of TB treatment. As a possible alternative, we therefore investigated the dynamics of neutrophil-derived soluble inflammatory mediators during TB treatment in relation to HIV ART status and the severity of lung impairment. Plasma samples of TB patients with (N = 47) and without HIV (N = 21) were analyzed at baseline, month 2, month 6 (end of TB treatment) and month 12. Plasma levels of MMP-1, MMP-8, MPO and S100A8 markedly decreased over the course of TB treatment and remained at similar levels thereafter. Post-TB treatment initiation, significantly elevated plasma levels of MMP-8 were detected in TB patients living with HIV, especially if they were not receiving ART treatment at baseline. Our data confirm that the plasma levels of neutrophil-based biomarkers can be used as candidate surrogate markers for TB treatment outcome and HIV-infection influenced MMP-8 and S100A8 levels. Future studies to validate our results and to understand the dynamics of neutrophils-based biomarkers post-TB treatment are needed.

Post-tuberculosis lung impairment: systematic review and meta-analysis of spirometry data from 14 621 people.

A substantial proportion of tuberculosis patients remain with pulmonary symptoms and reduced physical capacity despite successful treatment. We performed a systematic review to analyse the burden of post-tuberculosis lung impairment measured by lung function testing. We searched the PubMed database for articles published between database inception and November 2020 and performed meta-analyses to estimate the prevalence, type and severity of lung impairment among drug-susceptible and multidrug-resistant tuberculosis survivors. Methodological quality of included studies was assessed using the Newcastle-Ottawa scale. 54 articles were included in this review. For subjects with former drug-susceptible tuberculosis, the combined estimated mean was 76.6% (95% CI 71.6-81.6) of predicted for forced expiratory volume in 1 s (FEV1) and 81.8% (95% CI 77.4-86.2) for forced vital capacity (FVC). In former patients with multidrug-resistant tuberculosis, it was 65.9% (95% CI 57.1-74.7) for FEV1 and 76.0% (95% CI 66.3-85.8) for FVC, respectively. The analysis of impairment types in former patients with drug-susceptible and multidrug-resistant tuberculosis showed that 22.0% versus 19.0% had obstructive, 23.0% versus 22.0% restrictive and 15.0% versus 43.0% had mixed impairment type, respectively. In the majority of studies, at least 10-15% of tuberculosis survivors had severe lung impairment. This systematic review showed long-term abnormal spirometry results in a significant proportion of tuberculosis survivors.

Differences in clinical characteristics and quantitative lung CT features between vaccinated and not vaccinated hospitalized COVID-19 patients in Italy

BackgroundTo evaluate the differences in the clinical characteristics and severity of lung impairment, assessed by quantitative lung CT scan, between vaccinated and non-vaccinated hospitalized patients with COVID-19; and to identify the variables with best prognostic prediction according to SARS-CoV-2 vaccination status. We recorded clinical, laboratory and quantitative lung CT scan data in 684 consecutive patients [580 (84.8%) vaccinated, and 104 (15.2%) non-vaccinated], admitted between January and December 2021.ResultsVaccinated patients were significantly older 78 [69–84] vs 67 [53–79] years and with more comorbidities. Vaccinated and non-vaccinated patients had similar PaO2/FiO2 (300 [252–342] vs 307 [247–357] mmHg; respiratory rate 22 [8–26] vs 19 [18–26] bpm); total lung weight (918 [780–1069] vs 954 [802–1149] g), lung gas volume (2579 [1801–3628] vs 2370 [1675–3289] mL) and non-aerated tissue fraction (10 [7.3–16.0] vs 8.5 [6.0–14.1] %). The overall crude hospital mortality was similar between the vaccinated and non-vaccinated group (23.1% vs 21.2%). However, Cox regression analysis, adjusted for age, ethnicity, age unadjusted Charlson Comorbidity Index and calendar month of admission, showed a 40% reduction in hospital mortality in the vaccinated patients (HRadj = 0.60, 95%CI 0.38–0.95).ConclusionsHospitalized vaccinated patients with COVID-19, although older and with more comorbidities, presented a similar impairment in gas exchange and lung CT scan compared to non-vaccinated patients, but were at a lower risk of mortality.

Tuberculosis Treatment Response Monitoring by the Phenotypic Characterization of MTB-Specific CD4+ T-Cells in Relation to HIV Infection Status.

HIV infection causes systemic immune activation, impacts TB disease progression and hence may influence the diagnostic usability of Mycobacterium tuberculosis-specific T cell profiling. We investigated changes of activation and maturation markers on MTB-specific CD4+ T-cells after anti-tuberculosis treatment initiation in relation to HIV status and the severity of lung impairment. Thawed peripheral blood mononuclear cells from TB patients with (n = 27) and without HIV (n = 17) were analyzed using an intracellular IFN-γ assay and flow cytometry 2 and 6 months post-TB treatment initiation. H37Rv antigen was superior to the profile MTB-specific CD4+ T-cells phenotype when compared to PPD and ESAT6/CFP10. Regardless of HIV status and the severity of lung impairment, activation markers (CD38, HLA-DR and Ki67) on MTB-specific CD4+ T-cells declined after TB treatment initiation (p < 0.01), but the expression of the maturation marker CD27 did not change over the course of TB treatment. The MTB-specific T cell phenotype before, during and after treatment completion was similar between people living with and without HIV, as well as between subjects with severe and mild lung impairment. These data suggest that the assessment of activation and maturation markers on MTB-specific CD4+ T-cells can be useful for TB treatment monitoring, regardless of HIV status and the severity of lung disease.

Development of chronic lung impairment in Mozambican TB patients and associated risks

BackgroundPulmonary tuberculosis (PTB) is frequently associated with chronic respiratory impairment despite microbiological cure. There are only a few clinical research studies that describe the course, type and severity as well as associated risk factors for lung impairment (LI) in TB patients.MethodsA prospective cohort study was conducted at TB Research Clinic of Instituto Nacional de Saúde in Mavalane, Maputo, from June 2014 to June 2016. PTB patients were prospectively enrolled and followed for 52 weeks after TB diagnosis. Lung function was evaluated by spirometry at 8, 26 and 52 weeks after TB treatment initiation, and spirometric values of below the lower limit of normality were considered as LI. Descriptive statistical analysis was performed to summarize the proportion of patients with different lung outcomes at week 52, including type and severity of LI. Risk factors were analysed using multinomial regression analysis.ResultsA total of 69 PTB patients were enrolled, of which 62 had a valid spirometry result at week 52 after TB treatment start. At week 8, 26 and 52, the proportion of patients with LI was 78, 68.9 and 64.5%, respectively, and 35.5% had moderate or severe LI at week 52. The majority of patients with LI suffered from pulmonary restriction. Female sex, low haemoglobin and heavy smoking were significantly associated with LI.ConclusionModerate or severe LI can be observed in a third of cured TB patients. Further research is urgently needed to gain deeper insight into the characteristics of post TB LI, the causal pathways and potential treatment strategies.

Small Anellovirus in Hepatitis C Patients and Healthy Controls

To the Editor: Torquetenovirus (TTV) and torquetenominivirus (TTMV) are characterized by a small, negative-sense, circular, single-stranded DNA genome and by an extraordinary ability to produce chronic plasma viremia. Indeed, >80% of humans harbor variably high viral loads of TTV, TTMV, or both, in plasma, regardless of geographic provenance, age, sex, and health conditions (1). Currently, TTV and TTMV are classified as distinct species in the floating (although closely linked to the family Circoviridae) genus Anellovirus, but their extreme genetic heterogeneity and some distinctive features in genomic organization have led some to suggest that they should be classified as an independent family (2,3). Most recently, after examining serum specimens from patients with symptoms of an acute viral infection by using DNase sequence-independent single-primer amplification, Jones et al. (4) identified, among other viruses, 2 novel TTV- and TTMV-like agents. Because of their even smaller genomes (≈2.4 and 2.6 kb vs. 3.6–3.8 kb for TTV and 2.8–2.9 kb for TTMV), these agents were named small anelloviruses (SAVs). Because tissue culture and serologic methods are not yet available, diagnosis of anellovirus infection relies exclusively on viral DNA detection. We tested 55 Italian hepatitis C patients (mean age 56 ± 14 years, male/female ratio 30/25, 53 TTV positive) and, for comparison, 35 healthy donors (mean age 36 ± 12 years, male/female ratio 17/18, 33 TTV positive) for SAV in plasma by using the polymerase chain reaction (PCR) primers described by Jones et al. (4), followed by direct amplicon sequencing. To increase assay sensitivity, a heminested PCR format was adopted that used a sense primer designed in a segment of the untranslated region that is highly conserved among all anelloviruses (5´-TCAAGGGGC AATTCGGGCT-3´). We found 5 positive results among the hepatitis C patients (9.1%, all of whom were TTV positive) and 3 positive results among healthy controls (8.6%); and all were confirmed by sequence data. The amino acid sequences inferred from the coding segment of the amplicon of SAV in this study and the corresponding sequences of the 10 SAV in GenBank at the time of this writing were then aligned with representative TTV and TTMV sequences (Figure A1). This method allowed us to identify the motif WX7HX3CXCX5H, which is highly characteristic of the open reading frame 2 (ORF2) of anelloviruses (5), in all SAVs. SAV sequences, as well as a large number of TTVs and all TTMVs, were then used to construct a phylogenetic tree and to calculate the extent of genetic divergence within SAV, TTV, and TTMV. Although a precise phylogenetic description will require the analysis of full-length ORF2, the SAV sequences clustered quite separately from those of TTV and TTMV, and the extent of divergence observed among SAV was huge and in the same range as among TTV or TTMV. Furthermore, SAVs obtained from hepatitis C patients and healthy participants were intermingled (Figure A2). While this study was under way, Biagini et al. reported a 12% prevalence of SAV viremia in French blood donors (6). Our results confirm the high prevalence of SAV viremia in healthy persons and extend the finding to hepatitis C patients. Our data, combined with those of Biagini et al., indicate that, since SAV clusters separately from previously identified anelloviruses, it should be considered a distinct species (or possibly genus). This would increase the already high genetic diversity of anelloviruses, further arguing for the appropriateness of creating a separate viral family. Because the clinical and viral parameters of hepatitis C in SAV-positive patients were not significantly different from those in the SAV-negative patients (data not shown), our results suggest that, similar to TTV (7), SAV has little or no effect on the course of hepatitis C. Although anelloviruses have not yet been definitely linked to any specific disease, evidence is growing that they might be involved in acute respiratory diseases in children (8,9). Furthermore, a florid TTV replication in the respiratory tract correlated with severity of lung impairment in children with asthma (10). A precise appreciation of the wide range of viruses classified within the anelloviruses is a prerequisite to understanding such disease associations and the disease-inducing potential of these viruses in general.

Discrepancy between severity of lung impairment and seniority on the lung transplantation list

Background Organ allocation for lung transplantation, based mainly on accrued time on a waiting list, may not be an equitable system of organ allocation. To provide an objective view of the current practice concerning lung allocation, and timing for transplantation, we examined illness severity and list seniority in patients on a lung transplantation waiting list. Methods Adult patients awaiting lung transplantation underwent testing for mean pulmonary artery pressure (mPpa), maximum oxygen consumption (VO 2 max), 6-minute walk distance (6MWD), forced expiratory volume in 1 second, mean partial pressure of carbon dioxide, partial pressure of oxygen/fractional concentration of inspired oxygen, and diffusing capacity of the lung for carbon monoxide. Relationships between physiological variables and waiting list rankings were then determined. Results Thirty-four patients were tested and there was no correlation between time spent waiting on the list and mPpa (r = 0.01; P = .94), VO 2 max percentage predicted (r = 0.07; P = .71), or 6MWD (r = 0.15; P = .42). Many patients with functional impairments as indicated by low maximum VO 2 or by short 6MWD are scheduled to receive their transplant after patients with levels that indicate a lower degree of risk. When compared with a hypothetical reranking based on mean Ppa, 24 of the 34 patients (71%) on our current waiting list were found to be 5 positions higher or lower than this new risk-based ranking. Sixteen patients (47%) were 10 or more positions away from their hypothetical severity-based ranking, and 9 (26%) were at least 15 positions out of place. Sixteen of the 34 patients were ranked lower than they would be based on a severity of illness using the pulmonary artery pressure alone, 17 were ranked higher than “should be” based on pulmonary artery mean, and only 1 patient (ranked in position 15) was appropriately positioned based on seniority and severity of disease based on PA mean. Conclusion Rank order for lung transplantation has no relationship with illness severity, and the discrepancy between disease severity and seniority on the lung waiting list may compromise overall outcomes in the lung transplantation population.