Productive cough is an independent risk factor for the development of COPD in former smokers

Background and objective: It has yet to be determined whether the presence of productive cough is a risk factor for the development of COPD. The aim of the present study was to obtain more information on this potential association in Japanese men. Methods: Seven hundred and eighty‐three men with normal spirometry who did not have respiratory disease were recruited. The subjects were divided into three groups: group A, non‐smokers; group B, those with a positive smoking history without productive cough; and group C, those with a positive smoking history and productive cough. The incidence rates of COPD were compared among the three groups and the relative risks for the development of COPD were assessed. Results: During the mean follow‐up period of 33.6 ± 20.4 months, 19 (2.4%) subjects developed COPD. The incidence rate of COPD was significantly higher in group C than in group B (10.1 vs 2.2%, P = 0.003). A multivariate analysis of data for all subjects, current smokers and former smokers revealed that productive cough was an independent risk factor for the development of COPD in all subjects and former smokers but not in current smokers. Conclusions: Productive cough was an independent risk factor for the development of COPD in Japanese men. In particular, former smokers who complain of this symptom should be regarded as being at high risk for the development of COPD. The data suggested that stage 0 disease, as defined in the Global Initiative for Chronic Obstructive Lung Disease 2001 guidelines, is relevant for the identification of subjects at risk of developing COPD.     

Correlation between cough frequency and airway inflammation in children with primary ciliary dyskinesia

Cough is common in airway disease. We measured cough frequency in children with primary ciliary dyskinesia (PCD), to determine how accurately families assess this symptom; and to assess the relationship between cough frequency and airway inflammation, measured using induced sputum and exhaled nitric oxide (eNO). Twenty stable PCD children (7 boys), median age 10.8 years (interquartile range (IQR), 9-14), and 10 healthy control children, median age 12 years (IQR, 10.5-12.7), were recruited. ENO was measured using a chemiluminescence analyzer, with sputum induction with 3.5% saline. PCD children underwent ambulatory cough monitoring. Sputum neutrophils were higher in PCD (median, 70.3%; IQR, 55.3-78%) compared to controls (median, 27%; IQR, 24.5-33%; P = 0.004); cough frequency was higher (median episodes, 19; IQR, 11-22.5) compared to healthy children (median episodes, 6.7; IQR, 4.1-10.5; P < 0.001). Forced expiratory volume in 1 sec (FEV(1) percent predicted) and eNO were lower in PCD (median, 63%; IQR, 57-85%; P < 0.0001); eNO (median, 7.1 ppb (IQR, 4.8-19.1 ppb) vs. 12.4 ppb (IQR, 10.3-17.3 ppb), P = 0.043). Parental scoring of day and night cough correlated with recorded cough (r = 0.930, P < 0.0001, daytime; r = 0.711 for nighttime, P = 0.002). Visual analogue score and cough episodes also correlated positively (r = 0.906; P < 0.0001). There was a positive correlation between cough frequency and sputum neutrophil count in PCD (Spearman's r = 0.693, P < 0.002), but not percent FEV(1) or eNO. Stable PCD children have increased cough frequency and neutrophilic airway inflammation. In conclusion, cough frequency correlated with sputum neutrophils but not with FEV1 or eNO.     

Recurrent cough: Natural history and significance in infancy and early childhood

We investigated the outcome for a sample of children in whom recurrent cough was reported in the preschool years to determine (1) whether they shared the characteristics attributed to cough variant asthma, and (2) the proportion who developed classical wheezy asthma at follow-up during the early school years. A cohort of children identified as having recurrent cough in the preschool period was reassessed during the early school years. Previously identified asymptomatic preschool children who remained symptom-free provided a comparison group with respect to current respiratory symptoms, lung function, bronchial reactivity to inhaled methacholine, atopic status, peak flow variability, and recorded night cough. The response rate was modest, with 41% attending the follow-up study; information on current symptoms was available from a further 16%. Ascertainment of current symptoms showed that 70 of 125 (56.0% [95% CI 47.3–64.5%]) were symptom-free at follow-up, 46 (36.8% [28.7–45.5%]) continued to have recurrent cough in the absence of colds, and 9 (7.2% [3.6–12.8%]) reported recent attacks of wheeze. When comparing the 46 children whose recurrent cough persisted from the preschool period through to follow-up with subjects from the asymptomatic comparison group, the former had significantly more night cough (50.0% vs. 16.8%; P < 0.01), were more likely to be treated (10.9% vs. 1.7%; P = 0.01), or were diagnosed (26.1% vs. 5.7%; P < 0.001) as asthmatic. They also showed greater bronchial reactivity than their asymptomatic counterparts (1.23 mg/ml vs. 3.35 mg/ml; P = 0.002). Atopic status and other indices of lung function were similar between groups. We conclude that there are a group of children with long-term recurrent cough who display features consistent with a diagnosis of cough variant asthma, but at 2–4 years of follow-up, few progress to develop asthma characterized by wheeze. Pediatr Pulmonol. 1998; 26:256–261. © 1998 Wiley-Liss, Inc.     

Middle lobe syndrome: a nationwide study on clinicopathological features and surgical treatment

Introduction: Middle lobe syndrome (MLS) is a relatively uncommon lung disease that is characterized by damage to the middle lobe and often needs surgical intervention. Objective: To study clinical, radiological and histological features of all patients who underwent surgical resection for MLS in Iceland over a 13‐year period, including evaluation of surgical outcome. Methods: Information on patients who underwent surgery of the right middle lobe in Iceland from 1984 to 2006 was obtained from a centralized diagnosis and pathology registry. Clinical data were collected retrospectively from clinical records from hospitals and from private offices. All pathology specimens were reviewed. Results: We studied 18 patients, 3 males and 15 females between the ages 2 and 86 years (mean 55). The most common clinical features were recurrent infection (n = 15), chronic cough with productive sputum (n = 9), chest pain (n = 8) or dyspnea (n = 7). The most common findings on chest radiographs and on computerized tomography of the chest were atelectasis, consolidation and bronchiectasis. One patient had a foreign body. The most common major histological finding was bronchiectasis in nine patients, and two had foreign body reaction. Minor findings included bronchiolitis, organizing pneumonia and peribronchial inflammation. All patients survived surgery with minor peri‐ and postoperative complications. Conclusion: MLS is more common in females, and recurrent infections, chronic productive cough and dyspnea were the most common symptoms. Bronchiectasis is the most common histological finding. MLS can be treated effectively with lobectomy with low mortality and rate of complications. Please cite this paper as: Einarsson JT, Einarsson JG, Isaksson H, Gudbjartsson T and Gudmundsson G. Middle lobe syndrome: a nationwide study on clinicopathological features and surgical treatment. The Clinical Respiratory Journal 2009; 3: 77–81.     

Tracheobronchopathia osteochondroplastica: two cases and review of literature

Tracheobronchopathia osteochondroplastica (TO) is an unusual disorder. It mainly affects men over 50 years old and clinical manifestations are observed when obstructive or infectious complications occur. A 50-year old woman was investigated because of productive cough and 42 years old man was investigated because of haemoptysis. In two cases, at bronchoscopy, the typical picture of TO was observed. Microscopic examination of the biopsy material revealed bone formation. TO should be considered in the differential diagnosis as an unusual cause of chronic persistent cough, haemoptysis, persistent atelectasis, and recurrent segmental or lobar infection.     

A case of adalimumab-associated interstitial pneumonia with rheumatoid arthritis

Abstract

A 64-year-old woman with rheumatoid arthritis (RA) began to complain of recurrent non-productive cough 5 months after starting adalimumab. The chest radiograph and high-resolution computed tomographic findings revealed diffuse ground-glass attenuation. Her clinical course suggested that interstitial pneumonia (IP) may have been induced by adalimumab, and she was successfully treated with a medium dose of corticosteroid. This case indicates that adalimumab-associated IP should be considered if a RA patient develops non-productive cough following adalimumab therapy.     

Recurrence of thymoma accompanied with hypogammaglobulinemia 20 years after surgery: a case report]

We reported a case of recurrence of localized thymoma accompanied with hypogammaglobulinemia (Good's syndrome) 20 years after surgery. A 74-year-old man was admitted to this hospital because of mediastinal tumor and chronic pulmonary infection. He had been thymectomised at the age of 55 because of spindle cell thymoma. After that, he had been asymptomatic until January 1997, when he began to have a recurrent productive cough, and low-grade fever. Laboratory findings revealed hypogammaglobulinemia. Percutaneous needle biopsy of the mediastinal tumor revealed spindle cell thymoma. Therefore, hypogammaglobulinemia with thymoma (Good's syndrome) accompanied with a chronic lower respiratory tract infection was diagnosed. Immunologic studies revealed a marked decrease of CD 20 positive cells and decreased lymphocyte activation under the stimuli of phytohemagglutinin and concanavalin A. The thymoma was resected in Dec 1997, but the serum immunoglobulin showed no increase at al.     

Primary ciliary dyskinesia and humoral immunodeficiency – Is there a missing link?

BackgroundPrimary ciliary dyskinesia (PCD) and humoral mmunodeficiency (HID) are both rare disorders which cause recurrent upper and lower respiratory tract infections.ObjectiveTo examine the concurrence of PCD and HID in a patient cohort with known PCD.MethodsRetrospective review of the patient files.ResultsWe describe 11 patients of a cohort of 168 patients with PCD (6.5%) with a combination of PCD and some form of HID. The patients all presented with typical clinical symptoms for PCD, however the role of the concomitant immunological abnormalities is not clear.ConclusionPCD and HID coincided in 6.5% of the patients. We suggest that a common pathophysiological pathway results in both disorders.     

Case study: Idiopathic hemothorax in a patient with status asthmaticus

Introduction: Idiopathic spontaneous hemothorax has been rarely described in the literature. Case Study: A case of status asthmaticus and spontaneous hemothorax is described in a 29-year-old female of African descent who presented to the emergency room after 2 days of severe cough productive of yellow sputum, otalgia, sore throat, subjective fevers, chills, headache, progressive wheezing, chest tightness and dyspnea. She had a history of 7 years of asthma and was non-adherent with her controller asthma medications. Prophylactic subcutaneous administration of enoxaparin 40 milligrams was initiated upon hospitalization. The patient initially had a normal chest radiograph but subsequently developed a large, left hemothorax that required tube thoracostomy placement followed by video-assisted thoracoscopic surgery (VATS). Results: The patient was transferred to the Intensive Care Unit (ICU) and tube thoracostomy resulted in evacuation of 1,400 milliliters of blood-like fluid, which had a pleural fluid hematocrit greater than 50% of the serum hematocrit. A contrast-enhanced computed tomography (CT) scan of the chest did not reveal any source for the bleeding and a technetium bone scan of the chest was normal. The patient required transfusion of 5 units of packed red blood cells. She was then taken to the operating room for VATS because of continued chest tube drainage (3,200 milliliters of fluid over a 48-hour period). Conclusion: The etiology of the hemothorax was unknown despite surgical exploration but was felt to be secondary to cough and bronchospasm associated with status asthmaticus.     

Upper esophageal sphincter and esophageal motility in patients with chronic cough and reflux: assessment by high‐resolution manometry

The pathophysiology of chronic cough and its association with dsymotility and laryngopharyngeal reflux remains unclear. This study applied high‐resolution manometry (HRM) to obtain a detailed evaluation of pharyngeal and esophageal motility in chronic cough patients with and without a positive reflux–cough symptom association probability (SAP). Retrospective analysis of 66 consecutive patients referred for investigation of chronic cough was performed. Thirty‐four (52%) were eligible for inclusion (age 55 [19–77], 62% female). HRM (ManoScan 360, Given/Sierra Scientific Instruments, Mountain View, CA) with 10 water swallows was performed followed by a 24‐hour ambulatory pH monitoring. Of this group, 21 (62%) patients had negative reflux–cough SAP (group A) and 13 (38%) had positive SAP (group B). Results from 23 healthy controls were available for comparison (group C). Detailed analysis revealed considerable heterogeneity. A small number of patients had pathological upper esophageal sphincter (UES) function (n = 9) or esophageal dysmotility (n = 1). The overall baseline UES pressure was similar, but average UES residual pressure was higher in groups A and B than in control group C (?0.2 and ?0.8 mmHg vs. ?5.4 mmHg; P < 0.018 and P < 0.005). The percentage of primary peristaltic contractions was lower in group B than in groups A and C (56% vs. 79% and 87%; P = 0.03 and P < 0.002). Additionally, intrabolus pressure at the lower esophageal sphincter was higher in group B than in group C (15.5 vs. 8.9; P = 0.024). HRM revealed changes to UES and esophageal motility in patients with chronic cough that are associated with impaired bolus clearance. These changes were most marked in group B patients with a positive reflux–cough symptom association.     

RPGR mutations might cause reduced orientation of respiratory cilia

RPGR gene encodes retinitis pigmentosa guanosine triphosphatase regulator protein, mutations of which cause 70% of the X‐linked retinitis pigmentosa (XLRP) cases. Rarely, RPGR mutations can also cause primary ciliary dyskinesia (PCD), a multisystem disorder characterized by recurrent respiratory tract infections, sinusitis, bronchiectasis, and male subfertility. Two patients with PCD_RP and their relatives were analyzed using DNA sequencing, transmission electron microscopy (TEM), immunofluorescence (IF), photometry, and high‐speed videomicroscopy. The Polish patient carried a previously known c.154G>A substitution (p.Gly52Arg) in exon 2 (known to affect splicing); the mutation was co‐segregating with the XLRP symptoms in his family. The c.824 G>T mutation (p. Gly275Val) in the Australian patient was a de novo mutation. In both patients, TEM and IF did not reveal any changes in the respiratory cilia structure. However, following ciliogenesis in vitro, in contrast to the ciliary beat frequency, the ciliary beat coordination in the spheroids from the Polish proband and his relatives carrying the c.154G>A mutation was reduced. Analysis of the ciliary alignment indicated severely disturbed orientation of cilia. Therefore, we confirm that defects in the RPGR protein may contribute to syndromic PCD. Lack of ultrastructural defects in respiratory cilia of the probands, the reduced ciliary orientation and the decreased coordination of the ciliary bundles observed in the Polish patient suggested that the RPGR protein may play a role in the establishment of the proper respiratory cilia orientation. Pediatr Pulmonol. 2013; 48:352–363. © 2012 Wiley Periodicals, Inc.     

Detection of Hb Rothschild HBB: c.[112T>A or 112T>C], Through High Index of Suspicion on Abnormal Pulse Oximetry

We describe a case with a low oxygen affinity hemoglobin (Hb) variant who presented with cyanosis in the absence of cardiopulmonary disease. The patient, a 27-year-old pregnant female (P1G2), complained of a productive cough and bluish discoloration of the lips that started 3?days prior to seeking attention. She had no previous episodes and has generally been in good health. A positive family history of cyanosis was obtained in one sibling. Systematic examination, notably the cardiorespiratory system, revealed no abnormalities. The arterial Hb oxygen saturation (SpO₂) on pulse oximetry was 81.0% and Hb separation studies revealed an Hb variant identified as Hb Rothschild [β37(C3)Trp→Arg] (HBB: c.[112?T>A or 112?T>C]) by gene sequencing. The amino acid substitution (Trp→Arg) is an important contact point at the α1β2 interface and favors a T-quaternary state of the Hb tetramer. This leads to a low oxygen affinity state, which results in premature release of oxygen and drop in oxygen saturation. In the absence of cardiopulmonary disease, a decreased oxygen saturation reading, with or without cyanosis, should arouse suspicion for a possible dysHb.     

Cough ability measurements and recurrent respiratory symptoms in individuals with Ataxia Telangiectasia

Objectives: Ataxia-Telangiectasia (A-T) individuals often present with respiratory muscle weakness, causing recurrent respiratory system infections, asthma-like symptoms, and chronic cough life-threatening events. The cough flow volume maneuver may reveal powerless airflow needed for efficient cough. The study aims to explore cough ability in relation to the flow/volume maneuver. Methods: Data collected retrospectively from clinical charts of 35 A-T patients (age 12.7?±?4.9 years) included forced expiratory and cough flow/volume maneuvers performed on the same day. Analysis compared among the maneuvers matching indices, numbers of cough-spikes, flow rate decay, and the reference data of similar ages. Adjusted to age, BMI, and number of hospitalizations prior to the tests, values were correlated with the cough indices. Results: Cough peak-flow (C-PF) was propagated within 90?±?20?ms compared with peak expiratory flow (PEF?>?200?ms). C-PF measured values were higher than expiratory peak-flow measured values (3.27?±?1.53?L/s versus 3.02?±?1.52?L/s, respectively, but C-PF (%predicted) values were significantly lower than expiratory peak-flow (%predicted) (46?±?15 versus 68?±?20 %predicted, respectively, p?<?0.002). The number of spikes/maneuver was low when compared with reference (2.0?±?0.8 versus 6–12 spikes) and cough vital-capacity was lower than expiratory vital capacity (0.95?±?0.43 versus 1.03?±?0.47; p?<?0.01). Inefficient C-PF was more prevalent in patients suffering from recurrent respiratory illness. The length of wheelchair confinement duration mostly influenced the C-VC level. Conclusions: The cough flow–volume curve can be applied as a method to follow cough ability in patients with A-T who showed a significantly reduced cough capacity. Further studies are needed to establish if the findings may aid decisions regarding cough assistance.     

Primary ciliary dyskinesia. A new phenotypic variant

Primary ciliary dyskinesia (PCD) is a genetic disorder characterized by the inability of ciliated structures to beat effectively. Clinical course includes recurrent sinus and ear infections, chronic or recurrent bronchitis and infertility in men. Although several phenotypes have been described, lung function deterioration secondary to bronchiectasis becomes severe only rarely. That upper airway tract infections go unnoticed has not been reported. We report a case of PCD characterized by immotile sperm, severe obstructive respiratory disorder that required a sequential double lung transplant with the absence of recurrent sinus and ear infections.     

An Exploratory Analysis of Healthcare Costs and Utilization of Pediatric Patients with Crohn’s Disease

Objective To evaluate the healthcare costs and resource utilization associated with pediatric Crohn’s disease (PCD) from a payer perspective. Methods A retrospective analysis was conducted using claims from 1 January 2003 through 31 December 2006 from the HealthCare Partners database. Patients were younger than 18 years of age, had a new diagnosis of PCD, and continuous health plan eligibility 6 months before and 12 months after the disease index date (the date of the first claim with a PCD diagnosis). For comparison, a non-PCD cohort was matched on age, sex, and birthday (within 30 days). Results Data from 30 patients with PCD and 10,864 non-PCD controls were included. The total cost per member per month (PMPM) for the PCD cohort was 2,547 compared with2,547 compared with 101 for the non-PCD cohort. Inpatient admissions accounted for the largest portion (54%) of the total cost PMPM for PCD patients. There were 500 admissions per thousand members per year (PTMPY) for the PCD cohort and 11 admissions PTMPY for the non-PCD cohort. The average lengths of stay were 7.6 and 4.4 days for the PCD cohort and the non-PCD cohort, respectively, and the inpatient costs PMPM were 1,409 and1,409 and 18, respectively. Costs and resource utilization were also higher for PCD patients treated with systemic therapies. Conclusion PCD was associated with higher costs and resource utilization, compared with non-PCD controls, primarily driven by inpatient stays. Treating PCD appropriately before the disease progresses to a level requiring hospitalization may help reduce the costs associated with this disease.     

Influence of the rheological properties of airway mucus on cough sound generation

OBJECTIVES: There have been several reports regarding the role of airway mucus in cough sound generation, but the properties of the mucus that influence cough sound generation remain unclear. The aim of this study was to elucidate the influence of the rheological properties of airway mucus on cough sound generation. METHODOLOGY: The acoustic properties of voluntary cough sounds from 15 patients with chronic productive cough and nine controls with dry cough were analyzed by dividing the energy envelope of the sounds into three phases and computing the root mean square values and the duration of each phase as a proportion of the total cough duration. The rheological properties of the airway mucus (yield value, ciliary transportability and spinability) were also measured. Differences between productive and dry cough sounds, and correlations between the acoustic properties of cough sounds and the rheological properties of the airway mucus, were analyzed. RESULTS: The acoustic properties of productive and dry cough sounds differed significantly (P < 0.05). The acoustic properties of second phase cough sounds correlated significantly with the yield value and ciliary transportability of the airway mucus (P < 0.05). CONCLUSIONS: The rheological properties of the airway mucus influenced cough sound generation.     

Pancreatic Arteriovenous Malformation Associated with Duodenal Ulcer and H.Pylori Infection

Summary Pancreatic arteriovenous malformation (PAVM) is a rare condition that may cause duodenal ulcer. A 36-yr-old man with PAVM associated with duodenal ulcer and H.Pylori infection is described. The patient had recurrent episode of upper abdominal pain despite healed ulcer and H.Pylori eradication. The preoperative diagnosis was confirmed by computed tomography and the patient was treated with a pancreatoduodenectomy. Histological examination of the resected pancreas revealed a pancreatic arteriovenous malformation involving the adjacent duodenal wall.     

Sensitivity of the cough reflex in patients with chronic cough.

Cough may occur in association with excess bronchial secretions and may, therefore, be productive. However, in a proportion of patients the cough is non-productive and a possible association with an enhanced response of the cough reflex has been postulated. Using the irritant capsaicin, the sensitivity of the cough reflex was measured in 363 individuals. A questionnaire was used to divide subjects into three groups: Group A) non-coughing controls; Group B) subjects with non-productive cough; and Group C) subjects with productive cough. The group means (+/- 99% confidence interval (CI)) of the log capsaicin concentration causing two or more coughs (C2) for groups A, B, C were 0.98 (+/- 0.08), 0.64 (+/- 0.09) and 1.04 (+/- 0.23), respectively. The log capsaicin concentration causing five or more coughs (C5) for groups A, B, C were 1.78 (+/- 0.1), 1.16 (+/- 0.12) and 1.54 (+/- 0.25), respectively. Group B was significantly more sensitive to inhaled capsaicin than the other groups (p less than 0.01). No significant difference was observed between groups A and C. Some differences were found when subgroups were examined within groups B and C. In group B, patients with post-nasal drip were found to have a normal sensitivity of the cough reflex and were, therefore, different from the remainder of patients with non-productive cough. In group C, patients with bronchiectasis and current infection showed an increase in the sensitivity of their cough reflex. It is concluded that cough can occur in association with either excess mucus production leading to productive cough or an increase in the sensitivity of the cough reflex, possibly leading to non-productive cough.     

A case of adalimumab-associated interstitial pneumonia with rheumatoid arthritis

A 64-year-old woman with rheumatoid arthritis (RA) began to complain of recurrent non-productive cough 5 months after starting adalimumab. The chest radiograph and high-resolution computed tomographic findings revealed diffuse ground-glass attenuation. Her clinical course suggested that interstitial pneumonia (IP) may have been induced by adalimumab, and she was successfully treated with a medium dose of corticosteroid. This case indicates that adalimumab-associated IP should be considered if a RA patient develops non-productive cough following adalimumab therapy.     

Prevalence and natural history of potential celiac disease in adult patients

Abstract

Objective. Potential celiac disease (PCD) is a form of CD characterized by positive endomysial/tissue transglutaminase antibodies and a preserved duodenal mucosa despite a gluten-containing diet (GCD); it can evolve into flat, active CD. This evolution is, however, not certain. Our aim was to retrospectively study the prevalence and the natural history of adult patients with PCD. Methods. The clinical notes of all 47 patients with PCD attending our clinic between September 1999 and October 2011 were retrospectively reevaluated. To study their clinical features, patients with active CD, randomly selected and matched for sex and date of birth, served as controls. Symptoms, associated diseases, familiarity, and laboratory data at diagnosis were compared. Results. Prevalence of PCD among all celiac patients directly diagnosed in our center was 42/187, (1/4.4, 18.3%, 95% confidence interval (CI) 13.3–23.4%). Age at diagnosis, laboratory data, prevalence of symptoms, associated diseases, and familiarity for CD did not differ between patients with PCD and those with active CD. Some patients with PCD maintained a normal duodenal mucosa for many years and their symptoms spontaneously improved despite maintaining a GCD. Conclusions. PCD is not a rare form of CD. Having found no difference at all in age at diagnosis and clinical features between PCD and active CD could suggest that PCD is not a prodrome of CD but is a separate entity that can only subsequently evolve into active CD.