Characteristics of small airway disease in patients with HIV infection: insights from spirometry and impulse oscillometry.

RATIONALE: The respiratory system involvement is frequent in HIV patients, with airway diseases leading the non-infectious complications independent of smoking behaviour. Although spirometry is gold standard for diagnosing airway diseases, it can be false negative in small airway disease (SAD) when FEV1/FVC ratio is normal. Impulse Oscillometry (IOS) is a non-invasive method that can detect SAD even when the spirometry values are normal. This study aims to compare demographic and IOS parameters between patients with and without SAD and to establish optimal cut-off values for the IOS parameters. METHODS: Demographic data and HIV status were recorded for HIV patients under antiretroviral treatment without known airway disease. Spirometry was performed first, followed by Impulse Oscillometry (IOS). Patients with an MMEF value below 65% were defined as having spirometric small airway disease (SAD) and IOS parameters were compared between two groups. A ROC analysis was conducted to determine optimal cut-off values for IOS parameters according to Spirometric SAD. RESULTS: Mean age of 127 HIV patients was 43.4 and 62 of the patients were non-smoker. Spirometric SAD were seen 22% of non-smoker HIV patients. When demographic data were compared between groups with and without Spirometric SAD, age, smoking history and biomass exposure were significantly different. FEV1, FEV3, FEV6, FEV3/FEV6, FEV6/FVC, FEV3/FEVC values were also siginifacntly lower in the SAD group. R5, R5-R20, AX and Fres were significantly higher in the SAD group. When the ROC analysis was done, the R5-R20 cut-off determined as 0.08 for small airway disease based on MMEF, with a sensitivity of 71.8% and specificity of 58.1%. AX with a cut-off of 0.55 showed a sensitivity of 51.2% and specificity of 91.7%. CONCLUSION: This study highlights the frequence of small airway disease in HIV patients, particularly among 22% of non-smokers. Age, biomass exposure and smoking were possible risk factors for SAD. Impulse Oscillometry parameters, such as R5-R20 and AX, demonstrated promising diagnostic potential, with specific cut-off values established for identifying small airway disease. IOS can be an effective tool for the early detection of small airway disease in HIV patients and can allow early intervention for management of airway diseases.

Should asthma evaluation include assessment of small airway function?

Small-airways dysfunction associates with respiratory symptoms and clinical features of asthma: A systematic review

Chronic obstructive pulmonary disease (COPD) is associated with airflow limitation resulting from a combination of small airway disease (SAD) and parenchymal destruction. Although various diagnostic methods for SAD exist, access to these tools can be limited. This study aimed to explore the correlation between handgrip strength (HGS) and SAD in COPD patients. Cross-sectional prospective study. HGS was measured using a hand dynamometer. SAD was evaluated using impulse oscillometry, with results reported as the difference between respiratory resistance at 5 and 20 Hz (R5-R20). SAD was defined as R5-R20 ⩾0.07 kPa/L/s. The receiver operator characteristic (ROC) curves, sensitivity, and specificity values were calculated to determine the optimal cutoff value of HGS for predicting SAD. Sixty-four patients (90.6% male) were included. The average age was 72.1 ± 8.3 years, and body mass index was 23.4 ± 4.2 kg/m2. FEV1 was 71.6 ± 21.3%, and HGS was 30.2 ± 8.1 kg. R5-R20 was 0.11 ± 0.08 kPa/L/s. SAD was found in 64.1% of patients. A negative correlation between HGS and R5-R20 was observed (r = -0.332, p = 0.007). The best cutoff value for HGS in detecting SAD was determined to be 28.25 kg, with a sensitivity of 73.9%, specificity of 65.9%, and an area under ROC curve of 0.685 (95% CI 0.550-0.819, p = 0.015). SAD is common in COPD patients, and HGS is significantly negatively correlated with SAD. This tool might serve as an alternative or adjunctive assessment for small airway dysfunction in COPD patients. This study was registered with ClinicalTrials.gov with number NCT06223139.

Background/Objectives: Several studies have demonstrated the positive clinical and functional impact of adding Long-Acting Muscarinic Antagonist (LAMA) to Inhaled Corticosteroids (ICS) and Long-Acting Beta-Agonists (LABA) therapy in the treatment of severe asthma. Aim and objectives: To demonstrate that treating Small Airways Disease (SAD) in severe asthma patients who are candidates for biologics can improve respiratory symptoms, lung function, and airways inflammation, potentially avoiding or delaying the use of biological therapy. Methods: Thirty-two severe asthma patients with SAD were transitioned from separate inhalers for ICS/LABA and LAMA to extrafine single-inhaler beclomethasone, formoterol, and glycopyrronium. None of these patients underwent biological therapy before the study. Follow-up evaluations were conducted at baseline (T0) and three months after initiation (T3). Assessments included clinical evaluations, spirometry, oscillometry, and inflammation markers. Results: Transitioning to single-inhaler triple therapy from T0 to T3 resulted in significant improvements in Asthma Control Test (ACT) and SAD parameters, including increased Forced Expiratory Volume in the mid-range of lung capacity and improved airway resistance and reactance measurements using impulse oscillometry. A significant reduction in airway inflammation was evidenced by lower levels of Fractional Exhaled Nitric Oxide 350 (FeNO 350) (p < 0.001 for all). Conclusions: Adopting a single-inhaler triple therapy notably enhanced clinical control and small airway function in patients with severe asthma and SAD, supporting the positive impact of target-therapy for the achievement of a stable state termed “Quiet Asthma”.

Impulse oscillometry (IOS) is a sensitive tool for assessing small airway function in patients with chronic obstructive pulmonary disease (COPD). This study aimed to differentiate between COPD, small airway disease (SAD), and normal groups using IOS, and to evaluate the clinical applicability of IOS. This retrospective cohort study was conducted from January 2020 to February 2022. The eligible population comprised adult patients who simultaneously underwent IOS and pulmonary function tests. The diagnostic value of IOS in differentiating SAD and/or COPD from control was analyzed, and the correlations among IOS parameters, lung function, and radiological assessment results were determined. Among the enrolled 306 patients, 38 (12.4%) had SAD and 134 (43.8%) had COPD. The remainder comprised the control group without COPD and/or SAD. Abnormal airway resistance according to IOS parameters was detected in 17.2% of the patients in the control group, 47.2% of those in the SAD group, and 55.2% of those in the COPD group. Airway resistance estimated by IOS were significantly higher in the SAD and COPD groups than in the control group and correlated with lung function and radiological airway wall thickness. We developed a composite index called the IOS severity index (IOSsi) using IOS parameters that can predict SAD and COPD, and IOSsi showed significantly differentiation of SAD and/or COPD from control. Especially, IOSsi value ≥ 4 was associated with an increased risk of SAD and/or COPD and also with risk for moderate-to-severe exacerbation in patients with COPD. IOS may be a useful tool to differentiate disease status and evaluate disease severity and prognosis in patients with SAD and/or COPD, and a prognostic factor of COPD.

Impulse oscillometry (IOS) is a noninvasive technique that measures lung physiology independently of patient effort. In the present study, we aimed to investigate the utility of IOS parameters in comparison with pulmonary function testing (PFT) among hospitalized subjects, with emphasis on obstructive and small airway diseases. Sixty-one subjects hospitalized either with unexplained dyspnea or for pre-surgery evaluation were included in the study. All subjects underwent PFTs and IOS test. The correlation between IOS results and PFTs was examined in different subgroups. The ability of IOS parameters to predict abnormal PFTs was evaluated using the area under the receiver operating characteristic (ROC) curve, and optimal cutoff values were calculated. IOS results were found to correlate with PFT values. Subgroup analysis revealed that these correlations were higher in younger (age < 70) and non-obese (body mass index < 25kg/m2) subjects. The resonant frequency was an independent predictor and had the best predictive ability for abnormal FEV1/FVC (area under the ROC curve 0.732 [95% CI 0.57-0.90], optimal cutoff 17 Hz, 87% sensitivity, 62% specificity) and abnormal forced expiratory flow during the middle half of the FVC maneuver (area under the ROC curve 0.667 [95% CI 0.53-0.81], optimal cutoff 15 Hz, 77% sensitivity, 54% specificity). Area of reactance and the difference in respiratory resistance at 5 Hz and 20 Hz also showed a good predictive ability for abnormal FEV1/FVC (area under the ROC curve 0.716 and 0.730, respectively). We found that the IOS performed well in diagnosing small airway and obstructive diseases among hospitalized subjects. IOS might serve as an alternative to standard PFTs in non-cooperative or dyspneic hospitalized patients.

What Might Surviving Coronavirus Disease 2019 Look Like for People Living with HIV?

Aim Maximum mid-expiratory flow (MMEF) is one of the pulmonary function tests that report small airway disease. Our study aimed to investigate the role of MMEF values in asthma control, the prevalence of small airway disease, and their effect on asthma control in patients with asthma with normal forced expiratory volume in one second (FEV1) values. Material and Method Patients who presented to the Chest Diseases outpatient clinic of our hospital between 2018 and 2019 and were diagnosed as having asthma were included in the study. The characteristics of the patients, pulmonary function tests, their asthma treatment, and asthma control test (ACT) scores were recorded. Patients with FEV1 <80 in the pulmonary function test, those with additional lung disease, those who had an attack in the last 4 weeks, and patients who smoked were excluded from the study. MMEF <65 was defined as small airway disease. Results The MMEF% and MMEF (L/s) values of the group with uncontrolled asthma were found to be statistically significantly lower than those of the controlled asthma group (p = 0.016 and p = 0.003, respectively). MMEF% and MMEF (L/s) values in those with wheezing were found to be significantly lower compared with those without wheezing (p = 0.025 and p = 0.049, respectively). The MMEF% and MMEF (L/s) values of the patients with nocturnal symptoms were found to be statistically significantly lower than in patients without nocturnal symptoms (p = 0.023 and p = 0.041, respectively). ACT values of patients with MMEF <65 were found to be statistically lower than those of patients with MMEF >65 (0.047). Conclusion Considering small airway disease in patients with asthma may be beneficial in clinical practice.

BackgroundThe incidence of hypertension is high in people living with HIV (PLWH). High-sensitivity C-reactive protein (hsCRP), systemic inflammation response index (SIRI), and neutrophil-to-monocyte ratio (NMR) are considered economic and convenient parameters that reflect the levels of inflammation in patients. Our aim was to explore whether indirect inflammation markers are associated with hypertension in PLWH.MethodsThis was a case-control study. The case group (hypertension) comprised PLWH with hypertension, and the control group (non-hypertension) comprised sex- and age-(± 3 years)-matched PLWH without hypertension. Demographic parameters, hsCRP, neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), systemic immune- inflammation index (SII), SIRI, lymphocyte-to-monocyte ratio (LMR), platelet-to-neutrophil ratio (PNR), platelet-to-monocyte ratio (PMR), NMR, time to HIV diagnosis, antiretroviral therapy (ART) duration, recent CD4+ and CD8+ cell counts, recent CD4+/CD8+ ratio, recent HIV viral load (HIV-RNA),and recent ART regimen were obtained from the patients’ electronic medical records. A t-test or Wilcoxon rank-sum test was performed to compare differences between the two groups, and conditional logistic regression was used to analyze the risk factors of hypertension. Correlations between inflammation markers and CD4+ cell counts, CD8+ cell counts, and CD4+/CD8+ ratio were analyzed using Spearman’s correlation.ResultsIn the hypertension group, body mass index (BMI), hsCRP, NLR, SII, SIRI, NMR, time to HIV diagnosis, ART duration, CD4+ and CD8+ cell counts, and CD4+/CD8+ ratio, the ratio of HIV-RNA < 100 copies/mL were all higher than those in the non-hypertension group, while the PNR was lower than that in the non-hypertension group. ART duration, CD4+ cell counts, HIV-RNA < 100 copies/mL, hsCRP, SIRI, and NMR were positively associated with hypertensive risk in PLWH. CD8+ cell counts and CD4+/CD8+ ratio was negatively associated with hypertensive risk in PLWH. SIRI was negatively correlated with CD4+ cell counts and CD8+ cell counts, but positively correlated with CD4+/CD8+ ratio.ConclusionsWe identified positive associations between inflammation markers hsCRP, SIRI, NMR and hypertensive risk in PLWH. Alleviating inflammation may help control or delay the occurrence of hypertension in PLWH.

The response to treatment and progression of Chronic Obstructive Pulmonary Disease (COPD) varies significantly. Small airways disease (SAD) is being increasingly recognized as a key pathological feature of COPD. Studies have brought forward pathological evidence of small airway damage preceding the development of emphysema and the detection of obstruction using traditional spirometry. In recent years, there has been a renewed interest in the early detection of SAD and this has brought along an increased demand for physiological tests able to identify and quantify SAD. Early detection of SAD allows early targeted therapy and this suggests the potential for altering the course of disease. The aim of this article is to review the evidence available on the physiological testing of small airways. The first half will focus on the role of lung function tests such as maximum mid-expiratory flow, impulse oscillometry and lung clearance index in detecting and quantifying SAD. The role of Computed Tomography (CT) as a radiological biomarker will be discussed as well as the potential of recent CT analysis software to differentiate normal aging of the lungs to pathology. The evidence behind SAD biomarkers sourced from blood as well as biomarkers sourced from sputum and broncho-alveolar lavage (BAL) will be reviewed. This paper focuses on CC-16, sRAGE, PAI-1, MMP-9 and MMP-12.

Factors Associated With Coronavirus Disease 2019 Morbidity in a Cohort of People Living With Human Immunodeficiency Virus.

To quantify the incidence rate (IR) of diabetes in people living with HIV (PLWH), assess disparities relative to HIV-negative individuals and clarify the associations of antiretroviral therapy (ART) exposure and treatment duration with diabetes incidence. We searched PubMed up to July 20, 2025, for prospective cohort studies including PLWH aged ≥18 with ≥6 months of follow-up and reported diabetes incidence. Two reviewers independently assessed study quality using the Newcastle-Ottawa Scale and extracted data. A random-effects model estimated pooled incidence rates and subgroup differences. Meta-regression was performed to evaluate study-level associations between ART duration and diabetes incidence. Thirty-one studies contributed 1 230 314 person-years (PY) of follow-up. The IR in PLWH was 12.98 cases per 1000 PY (95% CI: 10.97-14.98). No significant difference was observed between PLWH (12.97 cases per 1000 PY) and HIV-negative individuals (12.67 cases per 1000 PY; p = 0.9597), although this comparison was based on a limited number of studies. However, incidence among PLWH on ART (14.05 cases per 1000 PY) was significantly higher than in those not on ART (7.42 cases per 1000 PY; p = 0.0179). Each year of ART exposure was associated with an increase of 0.354 cases per 1000 PY in univariable meta-regression (p = 0.008). In multivariable meta-regression, the association between ART duration and diabetes incidence remained significant after adjustment for mean age (p = 0.038), while age was also independently associated with higher incidence (p < 0.001). Diabetes incidence in PLWH is substantial and varies across regions and diagnostic definitions. Evidence comparing PLWH with HIV-negative individuals remains limited. ART exposure and longer ART duration are associated with higher diabetes incidence, highlighting the importance of routine metabolic screening in long-term HIV care.

IntroductionEarly initiation of antiretroviral therapy (ART) and adequate adherence are associated with sustained viral load (VL) suppression and effective treatment in people living with HIV (PLHIV). Enhanced adherence counseling (EAC) has been recommended for PLHIV on therapy with a VL >1000 copies/mL. We developed a digital application, "Samvaad," for counselors at ART centers to document the barriers to poor adherence and to provide thematic EAC for registered PLHIV under the aegis of the Mumbai District AIDS Control Society. The objectives of this study are to document the barriers to ART adherence in PLHIV who require EAC and to report the suppression outcomes in those who received EAC using Samvaad.MethodsThis study is a pre-post analysis of retrospective programmatic data from 674 PLHIV across 16 ART centers in Mumbai, India, from September 2020 to July 2022. We included only PLHIV who had unsuppressed VL and/or ART adherence <95% for the present analysis. The main outcome was the change in VL status, from unsuppressed at baseline to suppressed at follow-up assessment. We collected demographic information, ART-related information (duration of ART and type of ART regimen), and CD4 counts at the time of EAC. We also documented barriers to ART adherence using "Samvaad."ResultsThe mean (SD) age of PLHIV was 37.1 (9.9) years; 60.7% (n=409) were male, and 39.3% (n=265) were female. The most common barrier at baseline was "I have not been adequately informed about the dose and schedule of medications" (65.1% (n=439)), followed by "I do not have a fixed time to take my medicines" (63.2% (n=426)). The least common barriers were "I skip medications in the morning whenever I have alcohol the previous night" (4.2% (n=28)), "I skip medications whenever I have a fight with my partner/lover" (4.5% (n=30)), and "I live with a lot of people and hence I am unable to keep the ART medications at home" (4.5% (n=30)). The most common domains were "pill-taking practices" (68.3% (n=460)) and "ART knowledge/behavior" (67.7% (n=456)). At follow-up assessment, about 90% of PLHIV had suppressed VLs. In the multivariate analysis, males were significantly more likely to be virally suppressed compared with females (OR: 1.99, 95% CI: 1.07-3.68; p=0.029). PLHIV on third-line ART (OR: 0.30, 95% CI: 0.11-0.85; p=0.024) and those with the practices barrier domain (OR: 0.44, 95% CI: 0.22-0.90; p=0.024) were significantly less likely to achieve VL suppression at follow-up.ConclusionsThe majority of PLHIV in our study were between 26 and 45 years of age, were male, had been on ART for more than five years, and were on first-line ART. The main barriers were a lack of adequate knowledge about dosage and side effects, as well as not having a fixed schedule for taking pills. Viral suppression was reported in approximately 90% of PLHIV after EAC sessions. However, VL suppression was less likely in those who did not have a fixed time for taking medicines. This is a practical problem that needs to be addressed by developing treatment plans that consider time spent away from home or in transit. The development of a digital app was useful to document key barriers and domains in PLHIV with poor adherence and to provide thematic EAC at ART centers. The app can be used in urban as well as rural ART centers to provide client-centric thematic adherence counseling.

In recent decades, progress has been made worldwide in the prevention and control of HIV infection. What is the status of HIV prevention and control in China? This issue of HIV Medicine highlights the current progress in the management of and clinical research on HIV/AIDS in China, providing readers with a brief overview of this field. The Chinese authorities have made several efforts regarding the prevention and treatment of AIDS. For example, HIV infections transmitted by illegal blood transfusions have been eradicated, and HIV transmission among injecting drug users (IDUs) has been markedly reduced due to the implementation of a needle and syringe exchange programme. With the launch of the National Free Antiretroviral Treatment (ART) Program in 2003 and the subsequent implementation of the Four Free and One Care policy in 2006 [1], people living with HIV (PLWH) are often diagnosed via voluntary HIV testing or routine health examinations and provided free access to ART. The Four Free and One Care policy covers the provision of free ART to rural and urban residents without medical insurance; free voluntary counselling and HIV testing; free prevention of mother-to-child transmission; free schooling for orphaned children of PLWH; and care and economic assistance to PLWH with financial difficulties. In particular, the immediate initiation of ART in PLWH since 2016 has significantly reduced not only HIV transmission and prevalence but also AIDS-associated mortality [2]. Two studies in this issue analysed the clinical characteristics of patients receiving ART and pointed out the challenges faced by healthcare providers in China. Zhao et al. [3] presented the demographic and clinical characteristics of the national ART cohort for 2019. Their study showed great progress in increasing ART coverage and provided evidence of viral suppression across China. However, key populations of PLWH still face challenges: many are IDUs, have a history of treatment failure, or are co-infected with hepatitis C virus. Liu et al. [4] analysed the barriers to early diagnosis and timely ART initiation among PLWH, and their findings indicate the need for additional screening and intervention to improve the clinical management of HIV/AIDS. Co-infection with other viruses and bacteria among PLWH is associated with an increased incidence of failed immune reconstitution during ART and leads to a mortality rate higher than that associated with HIV infection alone. Two papers highlighted coinfections with hepatitis B virus (HBV) and Mycobacterium tuberculosis in PLWH. Jiang et al. [5] examined the factors associated with immune reconstitution in individuals with HIV/HBV co-infection receiving ART. They found that the baseline HIV viral load was the only significant factor that negatively influenced CD4 T-cell restoration in this population. Qi et al. [6] investigated tuberculosis (TB)-associated mortality within 90 days of admission and its risk factors among PLWH. Their data showed the 90-day mortality rate in patients with co-infection to be 13.6%, and early TB-associated death was associated with central nervous system TB, not receiving ART within 3 months after admission, and serum albumin levels < 25 g/L. In the era of ART, mother-to-child HIV transmission has substantially decreased. However, anti-HIV antibodies may still be detected in uninfected infants of mothers with chronic HIV infection. On monitoring the dynamics of anti-HIV antibodies in these infants, Liu et al. [7] noted the clearance of anti-HIV antibodies at more than 18 months post-delivery in 5.8% of uninfected children. These findings indicate that positive results for anti-HIV antibodies in infants aged 18–24 months should be carefully interpreted. Simultaneously, additional nucleic acid tests are necessary to confirm a diagnosis of HIV infection. Although ART has increased the life expectancy and improved the quality of life of PLWH, non-AIDS-associated events remain an issue. Lin et al. [8] summarized the clinical characteristics of non-AIDS-associated events involving multiple organs, such as the liver and kidneys, and suggested that multidisciplinary management is necessary for PLWH. Ying et al. [9] investigated the epidemiology, clinical features, and prognostic factors of HIV-associated talaromycosis and found an increased prevalence in Guangdong, China. Typical skin lesions were noted in 44.5% of patients. Induction therapy with azole alone was associated with a higher mortality than therapy with amphotericin B deoxycholate. These results may serve as a guide for clinicians in the management of HIV-associated talaromycosis. The viral reservoir is the biggest hurdle in the race to cure HIV/AIDS. In the shock and kill strategy, the latent HIV reservoir is maximally activated by stimulation with latency reversal agents and further cleared by host immune surveillance. Li et al. [10] evaluated the safety and efficacy of chidamide, a histone deacetylase inhibitor, for HIV-1 latency reversal in seven participants with viral suppression. All participants exhibited robust and repeated plasma viral rebound and increased cell-associated HIV-1 RNA levels, but only grade 1 adverse events were reported. Chidamide seems to be an effective agent in disrupting HIV-1 latency and reducing HIV-1 DNA loads; however, these findings need to be confirmed in randomized controlled clinical trials. Zhang et al. [11] summarized recent findings regarding the role of CD8 T-cells in controlling HIV infection, highlighting the differences between conventional antigen-specific and innate-like CD8 T-cells. Antiviral activity of CD8 T-cells in PLWH receiving ART may not be achieved via an antigen-specific approach, as HIV-specific CD8 T-cells can sense, but not effectively eliminate, cells harbouring intact proviruses. By contrast, virtual memory CD8 T-cells, a semi-differentiated subset of CD8 T-cells, may be involved in controlling the HIV DNA reservoir in patients receiving ART. In China, although remarkable progress has been made in controlling the HIV epidemic, challenges remain. First, the absolute number of PLWH is approximately 1.2 million, and the annual number of newly identified HIV/AIDS cases has been determined to be 150 000 in the last 3 years. In particular, approximately 31% of PLWH were diagnosed in the advanced stage, with peripheral CD4 T-cell counts of less than 200 cells/µL [3, 12]. In-time HIV screening is necessary to identify PLWH at an early stage. Second, the choice of ART drugs for PLWH is limited; for example, integrase inhibitors have recently been included in the free ART regimen, but this programme does not cover all PLWH. Third, sexual transmission has become the main route of HIV spread, and such transmission needs to be reduced by efficient preventive programmes, such as those providing universal pre-exposure prophylaxis. The 90-90-90 goals put forth by the Joint United Nations Program on AIDS/HIV seek for 90% of PLWH to be diagnosed, 90% of those diagnosed to receive ART, and 90% of those receiving ART to show viral suppression. It is feasible to achieve these 90-90-90 goals during next 5 years in China, but we still have a long way to go for the development of a cure for HIV infection.