{'fraction_non_alphanumeric': 0.02640914465904612, 'fraction_numerical': 0.017343318880567598, 'mean_word_length': 4.929906542056075, 'pattern_counts': {'":': 0, '<': 0, '<?xml version=': 0, '>': 0, 'https://': 0, 'lorem ipsum': 0, 'www.': 0, 'xml': 0}, 'pii_count': 0, 'substrings_counts': 0, 'word_list_counts': {'cursed_substrings.json': 0, 'profanity_word_list.json': 0, 'sexual_word_list.json': 0, 'zh_pornsignals.json': 0}}
Long-acting β-agonists with vs without inhaled corticosteroids for COPD.

Long-Acting β-Agonists With vs Without Inhaled Corticosteroids for COPD To the Editor In their observational study assessing the longterm outcomes associated with use of long-acting β-agonists (LABAs) in combination with inhaled corticosteroids (ICSs) in chronic obstructive pulmonary disease (COPD), Dr Gershon and colleagues1 reported that ICS use was not associated with pneumonia risk. This finding contradicts large randomized trials and observational studies, which have reported an increased risk of pneumonia with ICS use, particularly fluticasone.2-5 In the eAppendix, the authors made inaccurate assertions about our observational study,5 namely that “it only examined ICS and did not take into consideration use of LABA as our study did ... it studied people who died of pneumonia whereas ours did not, it examined pneumonia that occurred within 60 days of initiating ICS while our follow-up was about 21⁄2 years (indeed,whentheyextendedtheirobservationalperiodto180days, they also found no increased rate of pneumonia).” First, our study did take into consideration use of LABAs; 21% of the cases were using LABAs.5 Second, our study included mostly nonfatal hospitalized cases of pneumonia (19 667 of the 20 344 cases).5 Third, we studied pneumonia occurring at any time during ICS use, as in Figure 4, which showed that the risk of pneumonia was sustained with ICS use, remaining elevated during the first 5 years of continuing use.5 However, we also showed that ICS discontinuation led to a gradual disappearance of this risk of pneumonia over 180 days. We submit that the reason Gershon et al1 did not detect the well-established increased risk of pneumonia with ICS use is that the study design used an intent-to-treat approach in which ICS use was measured only at cohort entry. With pneumonia possibly occurring up to 5 or more years later, ICS exposure needed to be updated over time but was not. Supplemental eTable 5 shows that patients classified as users of ICS at cohort entry were exposed to ICS for only 47% of the days in the first year and 34% subsequently, whereas patients classified as nonusers of ICSs were exposed to ICSs for 6% of the days in the first year, increasing to 23% by year 5.1 Such excessive misclassification of exposure will attenuate high risks toward the null. Accordingly, this study, limited by its design, does not alter the evidence for the increased risk of severe pneumonia associated with ICS use in COPD.