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Antinuclear autoantibodies are more prevalent in COPD in association with low body mass index but not with smoking history

Background

Chronic obstructive pulmonary disease (COPD) is associated with a higher prevalence of antinuclear autoantibodies (ANAs). However, a significant subgroup of patients is ANA negative. It remains to be determined which patient groups carry autoantibodies.

 Methods

The association of smoking behaviour, disease status, gender, age and body mass index (BMI) with the presence of autoantibodies in the serum was determined in 124 patients with COPD and 108 non-COPD control subjects. In addition, the role of B cells in autoantibody generation in COPD was investigated by sequencing the antibody repertoire of B cells in the lungs of patients with COPD and of ex-smoking and never-smoking control subjects.

 Results

Patients with COPD had a significantly higher risk of being serum positive for ANAs (OR 3.12, 95% CI 1.68 to 5.76, p<0.001). ANAs were not significantly associated with age, smoking status, gender or pack-years of smoking. Within the COPD population, subjects with BMI <22 kg/m2 had a significantly higher risk of ANAs (OR 4.93, 95% CI 1.50 to 16.50, p=0.009) than those with normal or high BMI. The antibody repertoire of B cells in the lungs of patients with COPD had a high frequency of positively charged CDR3 residues, a feature which is associated with self-reactive antibodies.

 Conclusion

The results show that COPD is a heterogeneous disease with respect to the prevalence of ANAs. ANAs are primarily associated with the presence of COPD and with low BMI, but not with smoking and forced expiratory volume in 1 s.

Small Airway Disease in Asthma and COPD: Clinical Implications

Asthma and COPD have a high personal, societal, and economic impact. Both diseases are characterized by airway obstruction and an inflammatory process. The inflammatory process affects the whole respiratory tract, from central to peripheral airways that are <2 mm in internal diameter, the so-called small airways. There is an increased interest in small airway disease, and some new insights have been gained about the contribution of these small airways to the clinical expression of asthma and COPD, as reviewed in this article. Newly developed devices enable drugs to target the small airways, and this may have implications for treatment of patients with asthma, particularly those not responding to large-particle inhaled corticosteroids or those with uncontrollable asthma. The first studies in COPD are promising, and results from new studies are eagerly awaited.

Transtracheal Oxygen Therapy

Transtracheal oxygen therapy (TTO) has been used for long-term oxygen therapy for nearly 30 years. Numerous investigators have explored the potential benefits of TTO. Those results are reviewed in this article. TTO is best viewed not as a catheter but as a program for care. This article discusses patient selection for TTO. Publications evaluating complications are reviewed. In the past, a modified Seldinger technique (MST) was used for the creation of the tracheocutaneous fistula. The rather long program required for tract maturation with MST was labor-intensive and required substantial patient education and monitoring, particularly during the immature tract phase. Minor complications were not infrequent. More recently, the Lipkin method has been used to create a surgical tract under conscious sedation with topical anesthesia. The procedure is safe and well tolerated. Transtracheal oxygen is initiated the day following the procedure. Similarly, the tract matures in 7 to 10 days rather than the 6 to 8 weeks with MST. More rapid healing time and superior tract characteristics substantially reduce complications. The TTO program tailored for the Lipkin procedure is shortened, streamlined, and much less labor-intensive. Optimal outcomes with the TTO program require a committed pulmonologist, respiratory therapist, nurse, and surgeon (for the Lipkin procedure). This article discusses new directions in the use of transtracheal gas delivery, including the management of obstructive sleep apnea. Preliminary investigations regarding transtracheal augmented ventilation are presented. These include nocturnal use in severe chronic lung disease and liberation from prolonged mechanical ventilation.

Vitamin D Deficiency and Reduced Lung Function in Connective Tissue-Associated Interstitial Lung Diseases

Background:

Vitamin D is a steroid hormone with pleiotropic effects including immune system modulation, lung tissue remodeling, and bone health. Vitamin D deficiency has been implicated in the development of autoimmune diseases. We sought to evaluate the prevalence of vitamin D deficiency in a cohort of patients with interstitial lung disease (ILD) and hypothesized that vitamin D deficiency would be associated with an underlying connective tissue disease (CTD) and reduced lung function.

 Methods:

Patients in the University of Cincinnati ILD Center database were evaluated for serum 25-hydroxyvitamin D levels as part of a standardized protocol. Regression analysis evaluated associations between 25-hydroxyvitamin D levels and other variables.

 Results:

One hundred eighteen subjects were included (67 with CTD-ILD, 51 with other forms of ILD). The overall prevalence of vitamin D deficiency and insufficiency in the study population was 38% and 59%, respectively. Those with CTD-ILD were more likely to have vitamin D deficiency (52% vs 20%, P < .0001) and insufficiency (79% vs 31%, P < .0001) than other forms of ILD. Diminished FVC was associated with lower 25-hydroxyvitamin D3 levels (P = .01). The association between vitamin D insufficiency and CTD-ILD persisted (OR, 11.8; P < .0001) after adjustment for potential confounders. Among subjects with CTD-ILD, reduced 25-hydroxyvitamin D3 levels were strongly associated with reduced lung function (FVC, P = .015; diffusing capacity for carbon monoxide, P = .004).

 Conclusions:

There is a high prevalence of vitamin D deficiency in patients with ILD, particularly those with CTD-ILD, and it is associated with reduced lung function. Vitamin D may have a role in the pathogenesis of CTD-ILD.

Nonsteroidal Antiinflammatory Drugs May Affect the Presentation and Course of Community-Acquired Pneumonia

Background:

Nonsteroidal antiinflammatory drugs (NSAIDs) are commonly used as antipyretics and analgesics and may affect the host response to acute infection. We investigated the potential influence of NSAIDs on the presentation and short-term outcomes of nonimmunocompromised inpatients with community-acquired pneumonia (CAP) admitted to the ICU.

 Methods:

All consecutive patients with CAP admitted to the ICU or step-down unit of a university hospital during a 4-year period were prospectively included, except when receiving long-term NSAIDs or steroids. Drug exposures, presentation, and hospital course were recorded.

 Results:

Of the 90 patients included, 32 (36%) had taken NSAIDs prior to hospital referral. Compared with nonexposed patients, they were younger and had fewer comorbidities but similar severity of disease at presentation, despite a longer duration of symptoms before referral. However, they more often developed pleuropulmonary complications, such as pleural empyema and lung cavitation (37.5% vs 7%; P = .0009), and had a trend to more-invasive disease, with a higher frequency of pleural empyema (25% vs 5%, P = .014) and bacteremia, especially in those not having received concomitant antibiotics (69% vs 27%, P = .009). Nevertheless, the patients in the NSAID group had no more severe systemic inflammation or remote organ dysfunction. In multivariable analyses, NSAID exposure was independently associated with the occurrence of pleuropulmonary complications (OR, 8.1; 95% CI, 2.3-28).

 Conclusions:

Our findings suggest that NSAID exposure at the early stage of CAP is associated with a more complicated course but a blunted systemic response, which may be associated with a delayed diagnosis and a protracted course.

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