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  1. Wei Wei Ee
  1. NIHR Academic Clinical Fellow in Respiratory Medicine, King’s College London, London, UK
  1. Correspondence to Dr Wei Wei Ee, NIHR Academic Clinical Fellow in Respiratory Medicine, King’s College London, London, UK; weiwei.ee{at}nhs.net

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Does a brand-name inhaler provide better efficacy compared with its generic counterpart?

The clinical equivalence between generic and brand-name inhalers has yet to be determined. Moreover, there is a lack of comprehensive studies on specific populations affected by these products. To bridge this knowledge gap, Feldman et al 1 conducted a cohort study focusing on adults aged 40 and above diagnosed with chronic obstructive pulmonary disease (COPD). The research aimed to compare the effectiveness and safety of fluticasone-salmeterol inhalers (a combination therapy consisting of inhaled corticosteroids and long acting bronchodilator inhalers) in both its generic and brand-name forms.

A total of 45 369 patients were included in the study. Covariates were measured prior to the entry date and a propensity score model was employed to account for any confounding factors. The HR for experiencing the first COPD exacerbation was found to be similar between individuals using Wixela Inhub and Advair Diskus (HR 0.97 (95% CI 0.90 to 1.04)), indicating that there is no significant difference in incidence rates after considering confounding variables. Similarly, when examining hospitalisation due to pneumonia among the matched cohorts, no statistically significant difference in HR was observed (HR 0.99 (95% CI 0.86 to 1.15)). This study discovered that both inhalers exhibited comparable efficacy. However, it is important to note the wide CIs, indicating the necessity of longer-term follow-up in order to ensure equivalence.

Chronic and persistent breathlessness following COVID-19: aberrations in pulmonary function

Individuals recovering from COVID-19 frequently experience long-term persistent dyspnoea, despite displaying normal results on pulmonary function tests. To investigate this phenomenon, Noureddine et al 2 conducted a prospective observational cohort study. The authors examined the cardiopulmonary exercise capacities of patients who had been admitted to the intensive care unit due to severe COVID-19 infection. This study utilised cardiopulmonary exercise testing and evaluated lung function at rest as well as chestCT scans.

There was no significant correlation found between the length of intensive care unit (ICU) stay, dyspnoea, effort capacity or resting lung function parameters in the study. Cardiopulmonary exercise testing revealed that most patients had normal exercise capacity 12 months after severe COVID-19 pneumonia, with 80% of patients maintaining a peak oxygen uptake within normal limits. However, more than half of the participants experienced ventilatory inefficiency during exercise and an abnormal increase in physiological dead space ventilation. This impairment was particularly pronounced in patients with persistent dyspnoea, suggesting a potential contribution from ventilation inhomogeneity in post-COVID-19 dyspnoea.

The study revealed that 80% of the patients exhibited pulmonary abnormalities on CT chest, indicating a potential association between peak VD/Vt (dead space to tidal volume ratio) and predicted DLCO (diffusing capacity for carbon monoxide). This suggests the presence of microscopic fibrosis in the lung tissue, even though diffusion capacity at rest appeared normal. An interesting aspect to explore would be whether there are any notable disparities in cardiopulmonary exercise testing outcomes between patients who received corticosteroids (45%) and those who did not.

Saline nebulisers: does a higher concentration result in more favourable outcomes?

The effect of hypertonic saline on mucociliary clearance and sputum expectoration has been demonstrated in various studies. A randomised parallel-group trial called the saline at lower tonicity in cystic fibrosis (SALT-CF) trial was conducted in New South Wales, Australia to compare the effectiveness of different concentrations of nebulised saline in individuals with cystic fibrosis. Dwyer et al 3 divided participants into three intervention groups receiving 0.9%, 3% or 6% nebulised saline in a ratio of 1:1:1. The primary outcome assessed was the change in forced expiratory volume in the first second (FEV1) from baseline.

Among the 140 patients assessed, there were significant improvements in the FEV1 with both 3% and 6% hypertonic saline compared with 0.9% saline. There was no significant difference in treatment-related adverse events among all concentrations of nebulised saline. Both 3% and 6% saline also improved the time to first exacerbation and exercise capacity, but only 6% saline improved quality of life measures of physical functioning and global health perception. The authors concluded that 3% saline had some, but not all of the benefits of 6% saline for CF patients.

ICONIC study: reducing the target oxygen level leads to comparable mortality rates

Arterial hyperoxia and the liberal use of oxygen therapy have been associated with unfavourable functional outcomes in critically ill patients. The “ConservatIve versus CONventional oxygenation targets in Intensive Care patients” trial (ICONIC) is a randomised multicentre trial that compares conservative and liberal strategies for oxygen therapy in mechanically ventilated patients in the ICU. Van der Wal et al 4 conducted a randomised controlled trial involving 664 patients, with the primary endpoint being mortality at 28 days. At this time point, mortality rates were 38.5% (129/335) and 34.7% (114/329) in the low and high oxygen therapy groups, respectively, resulting in a risk ratio of 1.11 (95% CI 0.9 to 1.4; p=0.30).

Previous studies may have been limited by the lack of contrast between their target ranges. This study addressed this limitation by comparing two distinct oxygenation targets: low-oxygenation (PaO2 55–80 mm Hg or SpO2 91%–94%) and high-oxygenation (PaO2 110–150 mm Hg or SpO2 96%–100%). The absence of a mortality difference in this study should be considered as evidence against any potential benefits of a lower oxygen target for all patients. However, it is important to note that certain subgroups, such as those with severe acute respiratory distress syndrome (ARDS) and COPD, were excluded from this study. Additionally, given broad CIs, future trials with larger sample sizes are required.

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Footnotes

  • Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.

  • Competing interests None declared.

  • Provenance and peer review Commissioned; internally peer reviewed.